Funding, Deals & Partnerships: BIOLOGICS & MEDICAL DEVICES; BioMed e-Series; Medicine and Life Sciences Scientific Journal – http://PharmaceuticalIntelligence.com
A group of nearly 70 academic scientists, doctors, and biotech leaders sent a letter with an unusual request to the US Food and Drug Administration on Thursday: Please pay more attention to T cells, an overlooked part of the immune system that helps clear up viral infections.
COVID-19 Treatment and Vaccine Tracker This document contains an aggregation of publicly available information from validated sources. It is not an endorsement of one approach or treatment over another but simply a list of all treatments and vaccines currently in development.
Number
Type of Product – Treatment
FDA-Approved Indications (Treatments)
Clinical Trials
Ongoing for Other Diseases
Developer/ Researcher
Current Stage of Development
Funding Sources
Anticipated Timing
Sources
LEGEND
CCHF= Crimean-Congo Haemorrhagic Fever
CHIKV = Chikungunya Virus
DengV = Dengue Virus
FMD = Foot and Mouth Disease
EBOV = Ebola Virus
HAV = Hepatitis A Virus
HBV = Hepatitis B Virus
HIV = Human Immunodeficiency Virus
HPV = Human Papilloma Virus
Inf = Influenza
LASV = Lassa Fever Virus
MARV = Marburg Virus
MenB = Mengingitis B
MERS = Middle East Respiratory Syndrome
NIPV = Nipah Virus
NORV = Norovirus
RABV = Rabies Virus
RSV = Respiratory Syncytial Virus
RVF = Rift Valley Fever
SARS = Severe Acute Respiratory Syndrome
SIV = Simian Immunodeficiency Virus
TB = Tuberculosis
VEE = Venezuelan Equine Encephalitis Virus
VZV = Varicella Vaccine (Chickenpox)
YFV = Yellow Fever Virus
ZIKV = Zika Virus L
COVID-19 Treatment and Vaccine Tracker This document contains an aggregation of publicly-available information from validated sources. It is not an endorsement of one approach or treatment over another, but simply a list of all treatments and vaccines currently in development
Antibodies from recovered COVID-19 patients N/A Celltrion Pre-clinical Start Phase 1 ~ Sept 2020 Korea Herald 4
Antibodies from recovered COVID-19 patients N/A Vir Biotech/WuXi Biologics/Biogen Pre-clinical Stat News Vir Biotech 6
Antibodies from recovered COVID-19 patients N/A Lilly/Ab-Cellera (NIH Vaccines Research Center) Pre-clinical Start Phase 1 in late July 2020 Endpoints News
The worldwide endeavor to create a safe and effective COVID-19 vaccine is bearing fruit. Dozens of vaccines now have been authorized or approved around the globe; many more remain in development.
To clarify the landscape for our readers, our vaccine tracker has been split in two. The first chart details vaccine candidates that are still in development to address the lack of vaccines and access in many countries around the world; the second chart lists vaccines that are authorized or approved by one or more country. To reveal in-depth information about each candidate, select the “Details” button above the chart or click on the green plus button next to each entry.
Information about the unprecedented public/private partnerships spawned by the COVID-19 public health emergency now can be found below the charts.
Our charts are updated every other week. If you wish to submit an update or notice an issue with this data, please email Focus at news@raps.org.
Updated 28 January with new information on vaccines from Pfizer/BioNTech, Moderna, AstraZeneca, Gamaleya Research Institute, Janssen Vaccines, Sinovac, Bharat Biotech/Ocugen, Anhui Zhifei Longcom Biopharmaceutical, and Novavax as well as vaccine candidates from Walvax, Valneva, GSK/Sanofi, and Senai Cimatec.
Vaccine candidates in development
SHOW/HIDE DETAILS
Candidate
Mechanism
Sponsor
Trial Phase
Institution
Unnamed vaccine candidate
Recombinant vaccine (Sf9 cells)
WestVac Biopharma Co., Ltd.; West China Hospital; Sichuan University;
Phase 3
Jiangsu Province Centers for Disease Control and Prevention
Guangdong Provincial Center for Disease Control and Prevention; Gaozhou Municipal Center for Disease Control and Prevention; Zhuhai Livzonumab Biotechnology Co., Ltd.
Phase 3
Livzon Mabpharm Inc.
Razi Cov Pars
Recombinant vaccine (Spike protein)
Razi Vaccine and Serum Research Institute
Phase 3
Tehran Rasoul Akram Hospital; Karaj, Hesarak, Razi Vaccine and Serum Research Institute
GBP510
Nanoparticle vaccine
SK bioscience Co., Ltd.; GSK; University of Washington; CEPI
OWS:Operation Warp Speed is a collaboration of several US government departments including Health and Human Services (HHS) and subagencies, Defense, Agriculture, Energy and Veterans Affairs and the private sector. OWS has funded JNJ-78436735 (Janssen), mRNA-1273 (Moderna), and NVX‑CoV2373 (Novavax), V590 (Merck/IAVI), V591 (Merck/Themis), AZD1222 (AstraZeneca/University of Oxford), and the candidate developed by Sanofi and GlaxoSmithKline.
OWS is “part of a broader strategy to accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics.” Leaders of OWS say they could vaccinate as many as 20 million people by the end of the year and 100 million people by February.
ACTIV: Within OWS, the US National Institutes of Health (NIH) has partnered with more than 18 biopharmaceutical companies in an initiative called ACTIV. ACTIV aims to fast-track development of drug and vaccine candidates for COVID-19.
COVPN: The COVID-19 Prevention Trials Network (COVPN) combines clinical trial networks funded by the National Institute of Allergy and Infectious Diseases (NIAID): the HIV Vaccine Trials Network (HVTN), HIV Prevention Trials Network (HPTN), Infectious Diseases Clinical Research Consortium (IDCRC), and the AIDS Clinical Trials Group.
COVAX: The COVAX initiative, part of the World Health Organization’s (WHO) Access to COVID-19 Tools (ACT) Accelerator, is being spearheaded by the Coalition for Epidemic Preparedness Innovations (CEPI); Gavi, the Vaccine Alliance; and WHO. The goal is to work with vaccine manufacturers to offer low-cost COVID-19 vaccines to countries. CEPI’s candidates from companies Inovio, Moderna, CureVac, Institut Pasteur/Merck/Themis, AstraZeneca/University of Oxford, Novavax, University of Hong Kong, Clover Biopharmaceuticals, and University of Queensland/CSL are part of the COVAX initiative. The US joined COVAX on 21 January. The most up-to-date forecast of COVAX’s vaccine supply can be found here. An interim distribution forecast, most recently published 3 February, can be found here.
Moderna Vaccine Patent Application needs to include Names of Three NIH Scientists that Shared the Genome Sequence of SAR-Cov-2 with Moderna Early on
Reporter: Aviva Lev-Ari, PhD, RN
UPDATED on 11/12/2021
Within the filing, Moderna said it had “reached the good-faith determination” that three NIH scientists — John Mascola, Barney Graham and Kizzmekia Corbett — “did not co-invent” the sequence that prompts the body’s immune response to the coronavirus spike protein. The NIH, meanwhile, says the trio worked with Moderna at the outset of the pandemic to design the component in question.
In response to an Endpoints News request for comment, a Moderna spokesperson said the company has “all along” recognized the role the NIH played in developing the Covid-19 shot. But the spokesperson insisted only Moderna scientists invented mRNA-1273 — the codename for the company’s vaccine.
In the new book A Shot to Save the World out last month detailing the inventions of the mRNA Covid-19 vaccines, Wall Street Journal reporter Gregory Zuckerman wrote the three NIH scientists in question designed a sequence for a vaccine and sent it to Moderna. The biotech then used it to confirm their own designs and produce that vaccine.
Zuckerman wrote:
On Thursday, January 23, Wang packed his material in a container, trying hard to ensure it didn’t leak, and shipped it all to Kizzmekia Corbett, the government scientist who was doing similar work with other’s in Graham’s lab. Corbett, Graham and John Mascola chose an ideal spike-protein design and sent it to Moderna. The company’s scientists, relying on McLellan and Wang’s earlier work, had built their own spike-protein design. It matched the one from the government scientists, confirming they made the right choice. Moderna took their chosen sequence, employed some sophisticated computer software, and built an mRNA molecule capable of producing the stabilized spike protein. This would become Moderna’s vaccine antigen.
What Moderna says: The company argues that the NIH scientists — John Mascola, Barney Graham and Kizzmekia Corbett — were not part of selecting the messenger RNA sequence that became the Covid-19 shot authorized today. That sequence patent is essentially the heart of the product.
Moderna “has recognized the substantial role that the NIAID has played” in the vaccine development by including those scientists on other patents but “just because someone is an inventor on one patent application relating to our COVID-19 vaccine does not mean they are an inventor on every patent application relating to the vaccine,” it tweeted.
“Moderna remains the only company to have pledged not to enforce its COVID-19 intellectual property during the pandemic,” the company added.
It’s far from over: Moderna, which never brought a product to market before its effective Covid-19 shot, has received nearly $10 billion in government funding for the vaccine — a figure that advocates return to repeatedly when pressing for global access to patents and production.
SOURCE
From: POLITICO Pulse <pulse@email.politico.com> Reply-To: “POLITICO, LLC” <reply-fe8c1d737662017574-630320_HTML-638333449-1376319-0@politicoemail.com> Date: Friday, November 12, 2021 at 10:02 AM To: Aviva Lev-Ari <Avivalev-ari@alum.Berkeley.edu> Subject: Moderna vs. The Government
11/9/2021and 11/11/2021
The NIH told the New York Times earlier this week that three of its scientists — John Mascola, Barney Graham, who recently retired, and Kizzmekia Corbett, who has since moved over to Harvard — worked with Moderna to design the genetic sequence that prompts the vaccine to produce an immune response.
“I think Moderna has made a serious mistake here in not providing the kind of co-inventorship credit to the people who played a major role in the development of the vaccine that they are now making a fair amount of money on. We did our best to try to resolve this and ultimately failed but we are not done,” NIH Director Francis Collins told Reuters in an interview yesterday.
Dr. Barney Graham, left, and his colleague at the time, Dr. Kizzmekia Corbett, right, explaining the role of spike proteins to President Biden at the National Institutes of Health in Bethesda, Md., in February 2021
The vaccine grew out of a four-year collaboration between Moderna and the N.I.H., the government’s biomedical research agency — a partnership that was widely hailed when the shot was found to be highly effective. A year ago this month, the government called it the “N.I.H.-Moderna Covid-19 vaccine.”
The agency says three scientists at its Vaccine Research Center — Dr. John R. Mascola, the center’s director; Dr. Barney S. Graham, who recently retired; and Dr. Kizzmekia S. Corbett, who is now at Harvard — worked with Moderna scientists to design the genetic sequence that prompts the vaccine to produce an immune response, and should be named on the “principal patent application.”
If the three agency scientists are named on the patent along with the Moderna employees, the federal government could have more of a say in which companies manufacture the vaccine, which in turn could influence which countries get access. It would also secure a nearly unfettered right to license the technology, which could bring millions into the federal treasury.
“Omitting N.I.H. inventors from the principal patent application deprives N.I.H. of a co-ownership interest in that application and the patent that will eventually issue from it.”
According to the NYT article,
But experts said the disputed patent was the most important one in Moderna’s growing intellectual property portfolio. It seeks to patent the genetic sequence that instructs the body’s cells to make a harmless version of the spike proteins that stud the surface of the coronavirus, which triggers an immune response.
While it has not publicly acknowledged the rift until now, the Biden administration has expressed frustration that Moderna has not done more to provide its vaccine to poorer nations even as it racks up huge profits.
Comparative Study: Four SARS-CoV-2 vaccines induce quantitatively different antibody responses against SARS-CoV-2 variants
Reporter: Aviva Lev- Ari, PhD, RN
Marit J. van Gils, A. H. Ayesha Lavell, Karlijn van der Straten, Brent Appelman, Ilja Bontjer, Meliawati Poniman, Judith A. Burger, Melissa Oomen, Joey H. Bouhuijs, Lonneke A. van Vught, Marleen A. Slim, Michiel Schinkel, Elke Wynberg, Hugo D.G. van Willigen, Marloes Grobben, Khadija Tejjani, Jonne Snitselaar, Tom G. Caniels, Amsterdam UMC COVID-19 S3/HCW study group, Alexander P. J. Vlaar, Maria Prins, Menno D. de Jong, Godelieve J. de Bree, Jonne J. Sikkens, Marije K. Bomers, Rogier W. Sanders doi:https://doi.org/10.1101/2021.09.27.21264163
Abstract
Emerging and future SARS-CoV-2 variants may jeopardize the effectiveness of vaccination campaigns. We performed a head-to-head comparison of the ability of sera from individuals vaccinated with either one of four vaccines (BNT162b2, mRNA-1273, AZD1222 or Ad26.COV2.S) to recognize and neutralize the four SARS-CoV-2 variants of concern (VOCs; Alpha, Beta, Gamma and Delta). Four weeks after completing the vaccination series, SARS-CoV-2 wild-type neutralizing antibody titers were highest in recipients of BNT162b2 and mRNA-1273 (median titers of 1891 and 3061, respectively), and substantially lower in those vaccinated with the adenovirus vector-based vaccines AZD1222 and Ad26.COV2.S (median titers of 241 and 119, respectively). VOCs neutralization was reduced in all vaccine groups, with the largest (5.8-fold) reduction in neutralization being observed against the Beta variant. Overall, the mRNA vaccines appear superior to adenovirus vector-based vaccines in inducing neutralizing antibodies against VOCs four weeks after the final vaccination.
Figure 2:Binding and neutralization titers post-vaccination against VOCs.
(A) Median with interquartile range of binding titers to wild-type and VOCs S proteins represented as mean fluorescence intensity (MFI) of 1:100,000 diluted sera collected four-five weeks after full vaccination for the four vaccination groups. The lower cutoff for binding was set at an MFI of 10 (grey shading). Vaccine groups are indicated by colors with BNT162b2 in green, mRNA-1273 in purple, AZD1222 in orange and Ad26.COV2.S in blue. (B) Median with interquartile range of half-maximal neutralization (ID50) titers of D614G and VOCs pseudoviruses for sera collected after full vaccination for the four vaccination groups. The lower cutoff for neutralization was set at an ID50 of 100 (grey shading). Vaccine groups are indicated by colors with BNT162b2 in green, mRNA-1273 in purple, AZD1222 in orange and Ad26.COV2.S in blue. (C) Median ID50 neutralization of D614G and VOCs plotted against the reported vaccine efficacy against symptomatic infection2–5,12–17. Vaccine groups are indicated by colors with BNT162b2 in green, mRNA-1273 in purple, AZD1222 in orange and Ad26.COV2.S in blue. Circles represent WT data, squares for Alpha, diamond for Beta, nabla triangle for Gamma and delta triangle for Delta. Spearman’s rank correlation coefficient with p value are indicated. The result of the AZD1222 phase 3 trial conducted in South Africa, demonstrating poor (10%) efficacy against Beta variant, is not shown.
Reporter: Danielle Smolyar, Research Assistant 3 – Text Analysis for 2.0 LPBI Group’s TNS #1 – 2020/2021 Academic Internship in Medical Text Analysis (MTA)
An increase of infections among youth who are unvaccinated in countries with high vaccination rates is getting noticed in the role of young people in the pandemic.
On June 21 is Ross Ministry of health recommended that all individuals between the ages of 12 and 15 should be vaccinated. This makes the nation one of the few that have been approved vaccinations for younger kids. This decision came about in response too many other countries with high rates of vaccination are experiencing an increase in numbers of infections that are found to be in younger age groups.
Israel’s vaccination campaign which has reached to more than 85% of the adult population to be vaccinated noticed that case numbers are dropping around a dozen daily in the month of June. At the end of June, they have realized that the cases began to rise to more than 100 cases a day. These cases were found in kids under the age of 16 which is why the government decided to allow vaccinations.
Ran Balicer, and epidemiologists at Israel’s largest healthcare provider in Tel Aviv said that the younger profile is not surprising.
This trend that Israel started to notice is not just happening in Israel. The United States and the United Kingdom COVID-19, “become a disease of the unvaccinated, who are predominantly young”, says Joshua Goldstein, a demographer at the University of California, Berkeley. Stated in the article.
This trend has been occurring in the countries where the older population were being vaccinated first. Follow the drop in age because they were vaccinating older people who are the most at risk for the disease.
This shift has shut attention to the studies of transmission in the younger age groups. Karin Magnusson immunologist said that it has come very important to understand the burden of the disease among the younger children.
Magnusson on the impact of COVID-19 in children in Norway. On June 5 pre-print she reported that children see their doctor regularly up to six months after contracting Covid-19.
Balicer, is studying the virus spread in multi-generational households in Israel. Going beyond whether vaccinating children or not the patterns of COVID-19 infection have caused discussions about mask wearing to adolescence and kids in Israel.
As stated in the article, “As the burden of cases shifts towards younger people, arguments for vaccinating adolescents will become slightly more compelling,” agrees Nick Bundle, an epidemiologist at the European Centre for Disease Prevention and Control in Stockholm.” However, the risk of disease in children still is low and in other countries the total number of cases have declined.
Countries also need to consider the global contacts. As stated in the article, “Are we really better off giving the vaccine to kids in rich countries than to older people [in less wealthy countries] where it might have a much bigger impact on people’s lives?” says Jennie Lavine, who studies infectious-disease dynamics at Emory University in Atlanta, Georgia. “It seems hard for me to imagine a really good argument for that.”
Oh there is a downward shift and the average age of infected with COVID-19 in countries with high COVID-19 vaccination rates it may be short-lived. There could be a few scenarios where the shift could bounce back says Henrik Salje, who is an infectious disease epidemiologist at the University of Cambridge, UK. Many of the countries could start vaccinating the adolescence just like Israel and the United States are already doing so.
Bundle says that COVID- 19 can still be present in younger kids. “But how big a problem that is, is not a simple thing to respond to.”
Ramatroban, a Thromboxane A2/TPr and PGD2/DPr2 receptor antagonist for Acute and Long haul COVID-19
Author: Ajay Gupta, MD
From: “Gupta, Ajay” <ajayg1@hs.uci.edu> Date: Wednesday, July 7, 2021 at 1:10 PM To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu> Cc: “Dr. Saul Yedgar” <saulye@ekmd.huji.ac.il> Subject: Ramatroban, a Thromboxane A2/TPr and PGD2/DPr2 receptor antagonist for Acute and Long haul COVID-19
While corticosteroids may have a role in about 5% of hospitalized patients who have the cytokine storm, currently there is no effective treatment for mild or moderate COVID and long haul COVID. Massive increase in respiratory and plasma thromboxane A2 (TxA2) plays a key role in thromboinflammation and microvascular thrombosis, while an increase in respiratory and plasma PGD2 potentially suppresses innate interferon response, and acquired Th1 anti-viral response, while promoting a maladaptive type 2, anti-helminthic like immune response. Ramatroban is a potent dual receptor antagonist of Thromboxane A2/TPr and PGD2/DPr2 that has been used in Japan for the treatment of allergic rhinitis for past 20 years (Baynas®, Bayer Japan). We first disclosed use of ramatroban for COVID in a provisional patent application filed on 31st March, 2020; followed by the publication Gupta et al, J Mol Genet Med, 2020
Several experts, as outlined below in yellow highlighted text, have supported the idea of using ramatroban as an anti-thrombotic and immunomodulator in COVID-19.
1. Prof. Louis Flamand, Nicolas Flamand, Eric Boilard Laval Univ. Quebec, Canada: There is a lipid-mediator storm in COVID-19 characterized by massive increases in thromboxane A2 and PGD2 in the lungs and plasma. “Blocking the deleterious effects of PGD2 and TxA2 with the dual DPr2/TPr antagonist Ramatroban might be beneficial in COVID-19Archambault et al, FASEB, June 2021, doi: https://doi.org/10.1096/fj.202100540R
2. Prof. Garret A FitzGerald, Univ. Of Pennsylvania, Member National Academy of Sciences.https://en.wikipedia.org/wiki/Garret_A._FitzGerald “In the current pandemic there may be utility in targeting eicosanoids with existing drugs. These approaches would likely be most effective early in the disease before the development of ARDS, where cytokines and chemokines dominate. Dexamethasone limits COX-2 expression and might diminish COVID-19 severity and mortality at least in part, by diminishing COX metabolites… Dexamethasone might improve severe COVID-19 by diminishing the prostaglandins / thromboxane storm in the lungs”. “Treatment with a PGD2/DPr2 inhibitor decreased viral load and improved morbidity by upregulating IFN-lambda expression. ….. Antagonism of the thromboxane receptor (TPr) prevents ARDS…. Early administration of well-tolerated TPr antagonists may limit progress to severe COVID-19 (Theken and FitzGerald, Science, 2021)
4. Prof. Simon Phipps, Univ. of Queensland, Brisbane Australia “It has been hypothesized that DP2 antagonists be repurposed as a novel immunotherapy for the treatment of COVID-19, and this may be appropriate in mild to moderate cases where Th1 immunity is impaired.” (Ullah et al, Mucosal Immunology, 2021)
5. Prof. Bruce D. Hammock, Distinguished Professor, Univ of California Davis, Member US National Academy of Sciences and National Academy of Inventors; April 25, 2021. https://www.entsoc.org/fellows/hammock “I find your idea of blocking specific thromboxane receptors in preventing or reducing some of the devastating co-morbidity of COVID-19 very compelling. … A DPr2 receptor blocker is conceptually attractive in offering the potential of effective therapy and low risk due to a high therapeutic index.” E mail dated April 25, 2021.(https://ajp.amjpathol.org/action/showPdf?pii=S0002-9440%2820%2930332-1 and http://ucanr.edu/sites/hammocklab/files/328012.pdf)
6. Ann E Eakin, PhD, Senior Scientific Officer, NIH-NIAID “very compelling data supporting potential benefits of ramatroban in both reducing viral load as well as modulating host responses” E Mail dated Nov 20, 2020
Ramatroban is expected to reduce lung fibrosis in COVID-19 and therefore diminish clinical manifestations of Long haul COVID. Pang et al, 2021 “examined the effect of Ramatroban, a clinical antagonist of both PGD2 and TXA2 receptors, on treating silicosis using a mouse model. The results showed that Ramatroban significantly alleviated silica-induced pulmonary inflammation, fibrosis, and cardiopulmonary dysfunction compared with the control group.” https://www.thno.org/v11p2381.htm
Unfortunately, the animal models of COVID-19 are harsh, lack microvascular thrombosis and immune perturbations characteristic of human disease. These models may be good for testing antivirals but not for testing immunomodulators or anti-thrombotics. There is highly positive anecdotal experience with use of ramatroban in moderately severe COVID-19 (https://www.researchsquare.com/article/rs-474882/v1
Non-toxic antiviral nanoparticles with a broad spectrum of virus inhibition
Curator and Reporter: Dr. Premalata Pati, Ph.D., Postdoc
Non-toxic antiviral nanoparticles with a broad spectrum of virus inhibition
Infectious diseases account for 20% of global deaths, with viruses accounting for over a third of these deaths (1). Lower respiratory effects and human immunodeficiency viruses (HIV) are among the top ten causes of death worldwide, both of which contribute significantly to health-care costs (2). Every year, new viruses (such as Ebola) increase the mortality toll. Vaccinations are the most effective method of avoiding viral infections, but there are only a few of them, and they are not available in all parts of the world (3). After infection, antiviral medications are the only option; unfortunately, only a limited number of antiviral medications are approved in this condition. Antiviral drugs on a big scale that can influence a wide spectrum of existing and emerging viruses are critical.
The three types of treatments currently available are small molecules (such as nucleoside analogues and peptidomimetics), proteins that stimulate the immune system (such as interferon), and oligonucleotides (for example, fomivirsen). The primary priorities include HIV, hepatitis B and C viruses, Herpes Simplex Virus (HSV), human cytomegalovirus (HCMV), and influenza virus. They work mainly on viral enzymes, which are necessary for viral replication but which differ from other host enzymes to ensure selective function. The specificity of antivirals is far from perfect because viruses rely on the biosynthesis machinery for reproduction of infected cells, which results in a widespread and inherent toxicity associated with such therapy. However, most viruses mutate rapidly due to their improper replicating mechanisms and so often develop resistance (4). Finally, since antiviral substances are targeted at viral proteins, it is challenging to build broad-based antivirals that can act with a wide range of phylogenetic and structurally different virus.
Over the last decade breakthroughs in nanotechnology have led to scientists developing incredibly specialized nanoparticles capable of traveling in specific cells through a human body. A broad spectrum of destructive viruses is being targeted and not only bind to, but also destroy, by modern computer modeling technology.
An international team of researchers led by the University of Illinois at Chicago chemistry professor Petr Kral developed novel anti-viral nanoparticles that bind to a variety of viruses, including herpes simplex virus, human papillomavirus, respiratory syncytial virus, Dengue, and lentiviruses. In contrast to conventional broad-spectrum antivirals, which just prevent viruses from invading cells, the new nanoparticles eradicate viruses. The team’s findings have been published in the journal “Nature Materials.”
The goal of this new study was to create a new anti-viral nanoparticle that could exploit the HSPG binding process to not only tightly attach with virus particles but also to destroy them. The work was done by a group of researchers ranging from biochemists to computer modeling experts until the team came up with a successful nanoparticle design that could, in principle, accurately target and kill individual virus particles.
The first step to combat many viruses consists in the attachment of heparin sulfate proteoglycan on cell surfaces to a protein (HSPG). Some of the antiviral medications already in place prevent an infection by imitating HSPG’s connection to the virus. An important constraint of these antivirals is that not only is this antiviral interaction weak, it does not kill the virus.
Kral said
We knew how the nanoparticles should bind on the overall composition of HSPG binding viral domains and the structures of the nanoparticles, but we did not realize why the various nanoparticles act so differently in terms of their both bond strength and viral entry in cells
Kral and colleagues assisted in resolving these challenges and guiding the experimentalists in fine-tuning the nanoparticle design so that it performed better.
The researchers have employed advanced computer modeling techniques to build exact structures of several target viruses and nanoparticles up to the atom’s position. A profound grasp of the interactions between individual atom groupings in viruses and nanoparticles allows the scientists to evaluate the strength and duration of prospective links between these two entities and to forecast how the bond could change over time and eventually kill the virus.
Atomistic MD simulations of an L1 pentamer of HPV capsid protein with the small NP (2.4 nm core, 100 MUP ligands). The NP and the protein are shown by van der Waals (vdW) and ribbon representations respectively. In the protein, the HSPG binding amino acids are displayed by vdW representation.
Kral added
We were capable of providing the design team with the data needed to construct a prototype of an antiviral of high efficiency and security, which may be utilized to save lives
The team has conducted several in vitro experiments following the development of a prototype nanoparticle design which have demonstrated success in binding and eventually destroying a wide spectrum of viruses, including herpes simplex, human papillomaviruses, respiratory syncytial viruses and dengue and lentiviruses.
The research is still in its early phases, and further in vivo animal testing is needed to confirm the nanoparticles’ safety, but this is a promising new road toward efficient antiviral therapies that could save millions of people from devastating virus infections each year.
Cagno, V., Andreozzi, P., D’Alicarnasso, M., Silva, P. J., Mueller, M., Galloux, M., … & Stellacci, F. (2018). Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism. Nature materials, 17(2), 195-203. https://www.nature.com/articles/nmat5053
Other Related Articles published in this Open Access Online Scientific Journal include the following:
Rare earth-doped nanoparticles applications in biological imaging and tumor treatment
Reporter and Curator: Mr. Srinjoy Chakraborty (Junior Research Felllow) and Dr. Sudipta Saha, Ph.D.
Coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emerged as a serious global health issue with high transmission rates affecting millions of people worldwide. The SARS-CoV-2 is known to damage cells in the respiratory system, thus causing viral pneumonia. The novel SARS-CoV-2 is a close relative to the previously identified severe acute respiratory syndrome-coronavirus (SARS-CoV) and Middle East respiratory syndrome-coronavirus (MERS-CoV) which affected several people in 2002 and 2012, respectively. Ever since the outbreak of covid-19, several reports have poured in about the impact of Covid-19 on pregnancy. A few studies have highlighted the impact of the viral infection in pregnant women and how they are more susceptible to the infection because of the various physiological changes of the cardiopulmonary and immune systems during pregnancy. It is known that SARS-CoV and MERS-CoV diseases have influenced the fatality rate among pregnant women. However, there are limited studies on the impact of the novel corona virus on the course and outcome of pregnancy.
Figure: commonly observed clinical symptoms of COVID-19 in the general population: Fever and cough, along with dyspnoea, diarrhoea, and malaise are the most commonly observed symptoms in pregnant women, which is similar to that observed in the normal population.
The WHO and the Indian Council of Medical Research (ICMR) have proposed detailed guidelines for treating pregnant women; these guidelines must be strictly followed by the pregnant individual and their families. According to the guidelines issued by the ICMR, the risk of pregnant women contracting the virus to that of the general population. However, the immune system and the body’s response to a viral infection is altered during pregnancy. This may result in the manifestation of more severe symptoms. The ICMR guidelines also state that the reported cases of COVID-19 pneumonia in pregnancy are milder and with good recovery. However, by observing the trends of the other coronavirus infection (SARS, MERS), the risks to the mother appear to increase in particular during the last trimester of pregnancy. Cases of preterm birth in women with COVID-19 have been mentioned in a few case report, but it is unclear whether the preterm birth was always iatrogenic, or whether some were spontaneous. Pregnant women with heart disease are at highest risk of acquiring the infection, which is similar to that observed in the normal population. Most importantly, the ICMR guidelines highlights the impact of the coronavirus epidemic on the mental health of pregnant women. It mentions that the since the pandemic has begun, there has been an increase in the risk of perinatal anxiety and depression, as well as domestic violence. It is critically important that support for women and families is strengthened as far as possible; that women are asked about mental health at every contact.
With the available literature available on the impact of SARS and MERS on reproductive outcome, it has been mentioned that SARS infection did increase the risk of miscarriage, preterm birth and, intrauterine foetal growth restriction. However, the same has not been demonstrated in early reports from COVID-19 infection in pregnancy. According to a study that included 8200 participants conducted by the centre for disease control and prevention, pregnant women may be at a higher risk of acquiring severe infection and need for ICU admissions as compared to their non-pregnant counterparts. However, a detailed and thorough study involving a larger proportion of the population is needed today.
C.D.C. Reviewing Cases of Heart Problem in Youngsters After Getting Vaccinated and AHA Reassures that Benefits Overwhelm the Risks of Vaccination
Reporter: Amandeep Kaur, B.Sc. , M.Sc.
The latest article in New York times reported by Apoorva Mandavilli outlines the statement of officials that C.D.C. agency is investigating few cases of young adults and teenagers who might have developed myocarditis after getting vaccinated. It is not confirmed by the agency that whether this condition is caused by vaccine or not.
According to the vaccine safety group of the Centers for Disease Control and Prevention, the reports of heart problems experienced by youngsters is relatively very small in number. The group stated that these cases could be unlinked to vaccination. The condition of inflammation of heart muscle which can occur due to certain infections is known as myocarditis.
Moreover, the agency still has to determine any evidence related to vaccines causing the heart issues. The C.D.C. has posted on its website the updated guidance for doctors and clinicians, urging them to be alert to uncommon symptoms related to heart cases among teenagers who are vaccine recipients.
In New York, Dr. Celine Gounder, an infectious disease specialist at Bellevue Hospital Center stated that “It may simply be a coincidence that some people are developing myocarditis after vaccination. It’s more likely for something like that to happen by chance, because so many people are getting vaccinated right now.”
The article reported that the cases appeared mainly in young adults after about four days of their second shot of mRNA vaccines, made by Moderna and Pfizer-BioNTech. Such cases are more prevalent in males as compared to females.
The vaccine safety group stated “Most cases appear to be mild, and follow-up of cases is ongoing.” It is strongly recommended by C.D.C. that American young adults from the age of 12 and above should get vaccinated against COVID-19.
Dr. Yvonne Maldonado, chair of the American Academy of Pediatrics’s Committee on Infectious Diseases stated “We look forward to seeing more data about these cases, so we can better understand if they are related to the vaccine or if they are coincidental. Meanwhile, it’s important for pediatricians and other clinicians to report any health concerns that arise after vaccination.”
Experts affirmed that the potentially uncommon side effects of myocarditis get insignificant compared to the potential risks of SARS-CoV-2 infection, including the continuous syndrome known as “long Covid.” It is reported in the article that acute Covid can lead to myocarditis.
According to the data collected by A.A.P, about 16 thousand children were hospitalized and more than 3.9 million children were infected by coronavirus till the second week of May. In the United States, about 300 children died of SARS-CoV-2 infection, which makes it among the top 10 death causes in children since the start of pandemic.
Dr. Jeremy Faust, an emergency medicine physician at Brigham and Women’s Hospital in Boston stated that “And that’s in the context of all the mitigation measures taken.”
According to researchers, about 10 to 20 of every 1 lakh people each year develop myocarditis in the general population, facing symptoms from fatigue and chest pain to arrhythmias and cardiac arrest, whereas some have mild symptoms which remain undiagnosed.
Currently, the number of reports of myocarditis after vaccination is less than that reported normally in young adults, confirmed by C.D.C. The article reported that the members of vaccine safety group felt to communicate the information about upcoming cases of myocarditis to the providers.
The C.D.C. has not yet specified the ages of the patients involved in reporting. Since December 2020, the Pfizer-BioNTech vaccine was authorized for young people of age 16 and above. The Food and Drug Administration extended the authorization to children of age 12 to 15 years, by the starting of this month.
On 14th May, the clinicians have been alerted by C.D.C. regarding the probable link between myocarditis and vaccination. Within three days, the team started reviewing data on myocarditis, reports filed with the Vaccine Adverse Event Reporting System and others from the Department of Defense.
A report on seven cases has been submitted to the journal Pediatrics for review and State health departments in Washington, Oregon and California have notified emergency providers and cardiologists about the potential problem.
In an interview, Dr. Liam Yore, past president of the Washington State chapter of the American College of Emergency Physicians detailed a case of teenager with myocarditis after vaccination. The patient was provided treatment for mild inflammation of the inner lining of the heart and was discharged afterwards. Later, the young adult returned for care due to decrease in the heart’s output. Dr. Yore reported that still he had come across worse cases in youngsters with Covid, including in a 9-year-old child who arrived at the hospital after a cardiac arrest last winter.
He stated that “The relative risk is a lot in favor of getting the vaccine, especially considering how coronavirus vaccine have been administered.”
In the United States, more than 161 million people have received their first shot of vaccine in which about 4.5 million people were between the age 12 to 18 years.
Benefits Overwhelm Risks of COVID Vaccination, AHA Reassures
The latest statement of American Heart Association (AHA)/ American Stroke Association (ASA) on May 23rd states that the benefits of COVID-19 vaccination enormously outweigh the rare risk for myocarditis cases, which followed the C.D.C. report that the agency is tracking the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for myocarditis cases linked with mRNA vaccines against coronavirus.
The myocarditis cases in young adults are more often observed after the second dose of vaccine rather than the first one, and have more cases of males than females. The CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) observed such heart complications after 4 days of vaccination.
CDC reported that “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”
The CDC team stated that “The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection, and Strongly urged all young adults and children 12 years and above to get vaccinated as soon as possible.”
Even though the analysis of myocarditis reports related to coronavirus vaccine is in progress, the AHA/ASA stated that “myocarditis is typically the result of an actual viral infection, and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”
Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF) and former acting director of the CDC stated on ABC’s Good Morning America “We’ve lost hundreds of children and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis.” He added “still, from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine.”
After COVID-19 vaccination the symptoms that occur include tiredness, muscle pain, headaches, chills, nausea and fever. The AHA/ASA stated that “typically appear within 24 to 48 hours and usually pass within 36-48 hours after receiving the vaccine.”
All healthcare providers are suggested to be aware of the rare adverse symptoms such as myocarditis, low platelets, blood clots, and severe inflammation. The agency stated that “Healthcare professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly.”
President Mitchell S.V. Elkind, M.D., M.S., FAHA, FAAN, Immediate Past President Robert A. Harrington, M.D., FAHA, President-Elect Donald M. Lloyd-Jones, M.D., Sc.M., FAHA, Chief Science and Medical Officer Mariell Jessup, M.D., FAHA, and Chief Medical Officer for Prevention Eduardo Sanchez, M.D, M.P.H., FAAFP are science leaders of AHA/ASA and reflected their views in the following statements:
We strongly urge all adults and children ages 12 and older in the U.S. to receive a COVID vaccine as soon as they can receive it, as recently approved by the U.S. Food and Drug Administration and the CDC. The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection. According to the CDC as of May 22, 2021, over 283 million doses of COVID-19 vaccines have been administered in the U.S. since December 14, 2020, and more than 129 million Americans are fully vaccinated (i.e., they have received either two doses of the Pfizer-BioNTech or Moderna COVID-19 vaccine, or the single-dose Johnson & Johnson/Janssen COVID-19 vaccine).
We remain confident that the benefits of vaccination far exceed the very small, rare risks. The risks of vaccination are also far smaller than the risks of COVID-19 infection itself, including its potentially fatal consequences and the potential long-term health effects that are still revealing themselves, including myocarditis. The recommendation for vaccination specifically includes people with cardiovascular risk factors such as high blood pressure, obesity and type 2 diabetes, those with heart disease, and heart attack and stroke survivors, because they are at much greater risk of an adverse outcome from the COVID-19 virus than they are from the vaccine.
We commend the CDC’s continual monitoring for adverse events related to the COVID-19 vaccines through VAERS and VSD, and the consistent meetings of ACIP’s VaST Work Group, demonstrating transparent and robust attention to any and all health events possibly related to a COVID-19 vaccine. The few cases of myocarditis that have been reported after COVID-19 vaccination are being investigated. However, myocarditis is usually the result of a viral infection, and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine, especially since the COVID-19 vaccines authorized in the U.S. do not contain any live virus.
We also encourage everyone to keep in touch with their primary care professionals and seek care immediately if they have any of these symptoms in the weeks after receiving the COVID-19 vaccine:chest pain including sudden, sharp, stabbing pains;difficulty breathing/shortness of breath;abnormal heartbeat;severe headache;blurry vision;fainting or loss of consciousness;weakness or sensory changes;confusion or trouble speaking;seizures;unexplained abdominal pain; ornew leg pain or swelling.
We will stay up to date with the CDC’s recommendations regarding all potential complications related to COVID-19 vaccines, including myocarditis, pericarditis, central venous sinus thrombosis (CVST) and other blood clotting events, thrombosis thrombocytopenia syndrome (TTS), and vaccine-induced immune thrombosis thrombocytopenia (VITT).
The American Heart Associationrecommends all health care professionals be aware of these very rare adverse events that may be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, or symptoms of severe inflammation. Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly. As detailed in last month’s AHA/ASA statement, all suspected CVST or blood clots associated with the COVID-19 vaccine should be treated initially using non-heparin anticoagulants. Heparin products should not be administered in any dose if TTS/VITT is suspected, until appropriate testing can be done to exclude heparin-induced antibodies. In addition, health care professionals are required to report suspected vaccine-related adverse events to the Vaccine Adverse Event Reporting System, in accordance with federal regulations.
Individuals should refer to their local and state health departments for specific information about when and where they can get vaccinated. We implore everyone ages 12 and older to get vaccinated so we can return to being together, in person – enjoying life with little to no risk of severe COVID-19 infection, hospitalization or death.
We also support the CDC recommendations last week that loosen restrictions on mask wearing and social distancing for people who are fully vaccinated. For those who are unable to be vaccinated, we reiterate the importance of handwashing, social distancing and wearing masks, particularly for people at high risk of infection and/or severe COVID-19. These simple precautions remain crucial to protecting people who are not vaccinated from the virus that causes COVID-19.
Start Quote from European Medicines Agency document
Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 3-6 May 2021
News 07/05/2021
This month EMA’s safety committee (PRAC) reviewed a number of safety signals related to COVID-19 vaccines. The evaluation of safety signals is a routine part of pharmacovigilance and is essential to ensuring that regulatory authorities have a comprehensive knowledge of a medicine’s benefits and risks.
PRAC concludes review of signal of facial swelling with COVID-19 vaccine Comirnaty
PRAC has recommended a change to Comirnaty’s product information. After reviewing all the available evidence, including cases reported to the European database for suspected side effects (EudraVigilance) and data from the scientific literature, PRAC considered that there is at least a reasonable possibility of a causal association between the vaccine and the reported cases of facial swelling in people with a history of injections with dermal fillers (soft, gel-like substances injected under the skin). Therefore, PRAC concluded that facial swelling in people with a history of injections with dermal fillers should be included as a side effect in section 4.8 of the summary of product characteristics (SmPC) and in section 4 of the patient information leaflet (PIL) for Comirnaty. The benefit-risk balance of the vaccine remains unchanged.
PRAC concludes review of unusual blood clots with low blood platelets1 with Janssen’s COVID-19 vaccine
PRAC has now concluded its review of COVID-19 Vaccine Janssen and confirmed, as previously communicated, that the benefits of the vaccine in preventing COVID-19 outweigh the risks of side effects. In finalising the review, the Committee recommended on 20 April further refinement of the warning about thrombosis (formation of blood clots in the vessels) with thrombocytopenia (low blood platelets) syndrome, which was listed previously in the product information for COVID-19 Vaccine Janssen. The product information will now also include advice that patients who are diagnosed with thrombocytopenia within three weeks of vaccination should be actively investigated for signs of thrombosis. Similarly, patients who present with thromboembolism within three weeks of vaccination should be evaluated for thrombocytopenia. Lastly, thrombosis with thrombocytopenia syndrome will be added as an ‘important identified risk’ in the risk management plan for the vaccine. Furthermore, the marketing authorisation holder will provide a plan to further study the possible underlying mechanisms for these very rare events.
PRAC continues to closely review Comirnaty and COVID-19 Vaccine Moderna for unusual blood clots with low blood platelets2
The PRAC is closely monitoring whether mRNA vaccines might also be linked to cases of rare, unusual blood clots with low blood platelets, a side effect that has been reported in Vaxzevria and COVID-19 vaccine Janssen. Following a review of reports of suspected side effects, the PRAC considers at this stage that there is no safety signal for the mRNA vaccines. Only few cases of blood clots with low blood platelets have been reported. When seen in the context of the exposure of people to the mRNA vaccines, these numbers are extremely low, and their frequency is lower than the one occurring in people who have not been vaccinated. In addition, these cases do not seem to present the specific clinical pattern observed with Vaxzevria and COVID-19 Vaccine Janssen. Overall, the current evidence does not suggest a causal relation.
EMA will continue to monitor this issue closely and communicate further if necessary.
Topics of interests from enhanced monitoring of COVID-19 vaccines
Enhanced safety monitoring in the form of pandemic summary safety reports is one of the commitments required from the marketing authorisation holders in the context of the conditional marketing authorisation. Marketing authorisation holders are required to submit pandemic summary safety reports to EMA on a monthly basis. These reports are reviewed by the PRAC and any areaof concern further investigated, if needed.
PRAC assessing reports of Guillain-Barre syndrome with AstraZeneca’s Covid-19 vaccine
As part of the review of the regular pandemic summary safety reports for Vaxzevria, AstraZeneca’s Covid-19 vaccine, the PRAC is analysing data provided by the marketing authorisation holder on cases of Guillain-Barre syndrome (GBS) reported following vaccination. GBS is an immune system disorder that causes nerve inflammation and can result in pain, numbness, muscle weakness and difficulty walking. GBS was identified during the marketing authorisation process as a possible adverse event requiring specific safety monitoring activities. PRAC has requested the marketing authorisation holder to provide further detailed data, including an analysis of all the reported cases in the context of the next pandemic summary safety report.
PRAC will continue its review and will communicate further when new information becomes available.
PRAC assessing reports of myocarditis with Comirnaty and COVID-19 Vaccine Moderna
EMA is aware of cases of myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the membrane around the heart) mainly reported following vaccination with Comirnaty. There is no indication at the moment that these cases are due to the vaccine. However, PRAC has requested the marketing authorisation holder to provide further detailed data, including an analysis of the events according to age and gender, in the context of the next pandemic summary safety report and will consider if any other regulatory action is needed. Additionally, the PRAC has requested the marketing authorisation holder for COVID-19 Vaccine Moderna– also an mRNA vaccine – to monitor similar cases with their vaccine and to also provide a detailed analysis of the events in the context of the next pandemic summary safety report. EMA will communicate further when new information becomes available.
1Thrombosis with thrombocytopenia syndrome 2Thrombosis with thrombocytopenia syndrome
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