SARS-CoV-2 protease M^pro (NSP5), a key to COVID-19 therapy?

Pfizer announced promising clinical trials for their drug  Paxlovid (Owen et al., 2021), an inhibitor of the main SARS-CoV-2 protease, M^pro (3CL^pro, NSP5). In addition to being the main SARS-CoV-2 protease, Liu et al., (2021) discovered two different mechanisms whereby M^pro (NSP5) inactivates innate immunity.

ProSci applauds the work described in two recent publications regarding the synthesis, production, and utility of SARS-CoV-2 virus-like particles (VLPs).

Children have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and a substantially lower risk for developing severe coronavirus disease 2019 compared with adults.

However, the molecular mechanisms underlying protection in younger age groups remain unknown. 

Mistakes happen. It’s a fact of life, and when mistakes occur during cell replication, the body has mechanisms to catch these errors and destroy the defective cells. However, when this system fails, it can lead to tumor growth and to cancer.

Viruses use a variety of processes to evade the immune system and buy time to replicate. Some of these processes include inhibition of the humoral response, interfering, inhibiting, and modulating interferons, cytokines, chemokines, and apoptosis, as well as evading MHC. As viruses co-evolve with their hosts, they find new ways to evade detection.

The SARS-CoV-2 genome is ~29 kb divided into 10 open reading frames (ORFs). Each of these ORFs (except seemingly ORF10) is translated in 29 different proteins.

Cytokine Storm and COVID-19

Garnering mass attention due to the COVID-19 pandemic caused by the SARS-CoV-2 virus, the “cytokine storm” has been observed for decades. Cytokine storm refers to the overproduction of cytokines by the body in response to an infection. The production of cytokines is a normal part of the body’s immune response, but in some cases, the body tries to clear the infection so much so that the collateral damage done to the body is life-threatening. 

SARS-CoV-2 (COVID-19) Mutations

As viruses create more of themselves within a host, they are prone to copying errors. These mutations or recombinations are single point changes in the virus’ genetic code. This blog will be about the different mutations of SARS-CoV-2 we have been seeing recently.

The Effect of SARS-CoV-2 Vaccine Lasts At Least 4 Months

N Engl J Med reported the durability of immunity response of SARS-CoV-2 vaccine, mRNA-1273 (Moderna). The data was from 34 healthy adults with two vaccine injections. They have performed RBD binding assay and antibody neutralization assay, which revealed that there was no significant change in both RBD binding ability and neutralized inhibitory effect of antibodies over time. The results suggest that the effect of vaccination can last at least 4 months. (Widge et al., 2021)

Cell Paper: Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection

COVID-19 (SARS-CoV-2) is a major public heatlh threat with more than 1,200,000 deaths worldwide. The first stage in the coronavirus life cycle is viral entry where the viral spike protein will bind to a specific cell surface receptor. The spike proteins of SARS-CoV-2, as well as SARS-CoV-1 and NL63 use angiotensin-converting enzyme 2 (ACE2) as a receptor for binding. An antibody for this ACE2 protein has been produced by ProSci Inc. (Catalog No. 3217) that has been shown to function in immunohistochemistry and immunofluorescence experiments in human samples, and western blot experiments in human, mouse, and rat samples.