COVID-19 is still a global pandemic. Around the world, as of 5:40pm CEST, 20 June 2022, there have been 536,590,224 cumulative confirmed cases of COVID-19, including 6,316,655 deaths, reported to the World Health Organization. As of 16 June 2022, a total of 11,902,271,619 vaccine doses have been administered. The adoption of vaccines worldwide continues to increase, yet periodic spikes and surges in infection rates continue to occur with new SARS-CoV-2 variants, such as that observed in Australia over the past few months. Vaccine booster doses provide effective protection against developing severe disease and hospitalization, but vaccine adoption and distribution face ongoing challenges in low- and middle-income (LMIC) countries (1). Therapeutic interventions for those already infected are in development, with one (Paxlovid) currently available under emergency use authorization (EUA) in the US.
Cumulative COVID-19 statistics by country: WHO COVID-19 Dashboard. Geneva: World Health Organization, 2020. Available online: https://covid19.who.int/ (last cited: June 20, 2022).
In the rapidly shifting context of a pandemic, public health officials need a way to quickly assess how vaccinations perform in changing situations. One approach is to identify correlates of protection, or biological markers that correlate with a certain level of protection from disease. This tool is used to assess the design and formulation of annual influenza vaccines, as immune system markers that correlate with protection from flu can give developers a sense of how effective the vaccine might be for different population groups. Though they are not a replacement for rigorous clinical trials, correlates of protection can provide meaningful and predictive data for vaccine developers with smaller trial sizes and less time.
A study published in November 2021 indicated that levels of binding antibodies and neutralizing antibodies for the SARS-CoV-2 virus in blood serum are correlates of protection for Moderna, Inc.’s COVE phase 3 clinical trial of their mRNA COVID-19 vaccine.
Severe acute respiratory syndrome (SARS) is a viral respiratory disease caused by a SARS-associated coronavirus. The most recent version, SARS-CoV-2 was first detected in China in the winter of 2019 and is responsible for the current COVID-19 (coronavirus disease 2019) global pandemic. This virus and its variants have resulted in over 200 million infections and more than 4 million fatalities world-wide. To combat this deadly outbreak the global research community has responded with remarkable swiftness with the development of several vaccines and drug therapies, all produced in record time. In addition to vaccines and drug therapies, diagnostic kits and research reagents continue to roll out to track infections and to help find additional therapies.
This peer-reviewed paper published in Nature Scientific Reports by Alves and colleagues demonstrates how a new assay can be used to discover novel inhibitors that block the binding of SARS-CoV-2 to the human ACE2 receptor as well as study how mutations in the SARS-CoV-2 Spike protein alter its apparent affinity towards human ACE2. The paper also details studies where the assay is used to detect the presence of neutralizing antibodies from both COVID-19 positive samples as well as samples from vaccinated individuals.
Wearing blue surgical gowns and white respirator hoods, research scientist Pradeep Uchil and post-doctoral fellow Irfan Ullah carry an anesthetized mouse to the lab’s imaging unit. Two days ago, the mouse was infected with a SARS-CoV-2 virus engineered to produce a bioluminescent protein. After an injection of a bioluminescence substrate, a blue glow starts to emanate from within the mouse’s nasal cavity and chest, visible to the imaging unit’s camera and Uchil’s eyes.
“We were never able to see this kind of signal with retrovirus infections.” Uchil is a research scientist at the Yale School of Medicine whose work focuses on the in vivo imaging of retroviral infections. Normally, the mouse would have to be sacrificed and “opened up” for viral bioluminescent signals from internal tissues to be imaged directly.
A year after COVID-19 was declared a pandemic, collaborative efforts among pharma/biotech and academic researchers have led to remarkable progress in vaccine development. These efforts include novel mRNA vaccine technology, as well as more conventional approaches using adenoviral vectors. While vaccine deployment understandably has captured the spotlight in the fight against COVID-19, there remains an urgent need to develop therapeutic agents directed against SARS-CoV-2.
In the March 12 issue of Science, an editorial by Dr. Francis Collins, director of the U.S. National Institutes of Health (NIH), examines lessons learned over the past 12 months (1). Collins points out that many clinical trials of potential therapeutics were not designed to suit a public health emergency. Some were poorly designed or underpowered, yet they received considerable publicity—as was the case with hydroxychloroquine. Collins advises developing antiviral agents targeted at all major known classes of pathogens, to head off the next potential pandemic before it becomes one. A news feature in the same issue discusses the current state of coronavirus drug development (2).
The present crop of drug candidates is remarkably diverse, including repurposed drugs that were originally developed to treat diseases quite different from COVID-19. Typically, however, the mainstream candidates belong to two broad classes: small-molecule antiviral agents and large-molecule monoclonal antibodies (mAbs).
COVID-19 vaccine distribution efforts are underway in several countries. Recently, the Serum Institute of India celebrated the nationwide rollout of its Covishield vaccine, kicking off the country’s largest ever vaccination program. Meanwhile, many other vaccines against the coronavirus that causes COVID-19 are in either preclinical studies or clinical trials. At present, 19 vaccine candidates are in Phase 3 clinical trials, while 8 vaccines have been granted emergency use authorization (EUA) in at least one country.
The global war against the coronavirus that causes COVID-19 rages on, spearheaded by efforts to develop effective and safe vaccines. At the time of writing, over 100 COVID-19 vaccine clinical trials were listed in the clinicaltrials.gov database. Recent attention has focused on mRNA vaccines developed by Pfizer/BioNTech and Moderna. If licensed, they would become the first mRNA vaccines for human use.
The SARS-CoV-2 nucleocapsid protein accounts for the largest proportion of viral structural proteins and is the most abundant protein in infected cells. Nucleocapsid proteins have the job of “packaging” the viral nucleic acid (in this case, RNA). Viral nucleocapsid proteins can also enter the host nucleus and interact with a variety of host proteins to interfere with critical processes of the host cell, including protein degradation. Here we review a study that used an in vitro protein degradation assay to investigate the interaction of the SARS-CoV-2 nucleocapsid protein and the proteasome activator PA28γ.
In SARS-CoV-2 infections, the nucleocapsid protein is critical for infection, replication and packaging. The SARS-CoV-2 nucleocapsid protein is not only localized in the cytosol of the host cell but also is translocated into the nucleus. There, it interacts with various cellular proteins that modulate cellular functions, such as the degradation of unneeded or damaged proteins by proteolysis. Researchers have proposed that the protein degradation system plays an important part in coronavirus infection (1).
This post was written by guest blogger, Nitin Kapoor, from our Promega India branch office.
The COVID-19 crisis has led to substantial worldwide efforts to develop drug treatments and vaccines effective against SARS-CoV-2. Termed a novel Coronavirus, SARS-CoV-2 belongs to the same family as that of SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) viruses that were responsible for epidemics in 2003 and 2012 respectively (Lu et al. 2020)
In the nine months since the first cases of COVID-19 were noticed in Wuhan, China, the virus has spread around the globe and infected over 22 million people. As with all emerging infectious diseases, we often find ourselves with more questions than answers. However, through the tireless work of researchers, doctors and public health officials worldwide, we have learned a lot about the virus, how it spreads and how to contain it.
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