Three Years of Coronavirus: The Search for a Broad-Acting Antiviral

Three Years of Coronavirus: The Search for a Broad-Acting Antiviral

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Three Years of Coronavirus

We have just passed the three-year anniversary of the outbreak of the coronavirus pandemic caused by SARS-CoV-2. This pandemic will define a generation not only socially, but scientifically, as researchers in immunology, virology, and epidemiology were galvanized to solve the puzzling biomedical mysteries around COVID-19 infections.

Even with the unprecedented speed of SARS-CoV-2 research, including vaccine development, new discoveries, and questions are still flooding the scientific community. As SARS CoV-2 is now heading toward endemic virus territory alongside influenza and rhinoviruses, one of the most important continuing research areas is in identifying the molecular mechanisms of susceptibility to the virus to inform innovations in antiviral development.

Virus-Directed VS Host-Directed Treatments

Vaccines against SARS-CoV-2 are only the first line of defense against COVID-19 infections. The combination of regions with low vaccination rates and continued viral evolution creates an important role for COVID-19 treatments in addition to preventives. The currently available antivirals are remdesivir and molnupiravir, which target the virus’ polymerase, and paxlovid, which targets the viral protease.

While much is understood about viral biology, a therapeutic research area called host-directed therapeutics is a promising approach to circumvent challenges like drug resistance. In contrast to vaccines, which mimic infection to “train” the immune system to respond to a virus, and antivirals, which target the underlying biology of the virus, host-directed therapeutics target features of the host’s biology to treat the infection. The hope is that this will provide broader activity by targeting mechanisms common to the human response to multiple variants of the same virus, if not multiple types of virus.

Chromatin Remodeling Complexes Regulate COVID-19 Infection

In 2020, a research group at Yale performed a genome-wide CRISPR screen to identify important host genes involved in SARS-CoV-2 infection. Published in Cell, the study identified a number of critical genes that increased susceptibility to infection, notably several subunits of the mammalian SWItch/Sucrose Non-Fermentable complex (mSWI/SNF, pronounced “switch/sniff”). The mSWI/SNF complex is a chromatin-remodeling complex, meaning it regulates accessibility to the genome and thus, which genes are expressed.

In a paper published last week in Nature, the same group explored this finding in-depth, uncovering a new host-directed therapeutic target for a broad-acting antiviral against SARS CoV-2, emerging variants, and drug-resistant variants. One of the mSWI/SNF subunits, SMARCA4, has essential catalytic activity for ACE2 chromatin accessibility, ACE2 being the receptor bound by SARS CoV-2 for cellular entry.

The authors found that using a small-molecule inhibitor of mSWI/SNF activity conferred resistance to multiple SARS CoV-2 variants, including a redeliver-resistant strain, in three cell lines and three primary human cell types including airway epithelial cells, the most common target of the virus. This is a hugely promising approach to developing new broad-acting antivirals to combat viral evolution, drug resistance, and the continued global circulation of SARS-CoV-2.

Outsourcing Bioinformatics Analysis: How Bridge Informatics Can Help

Spanning virology, immunology, and beyond, our clients are tackling their biological research questions using sophisticated approaches in bioinformatics and many more cutting-edge tools. As experts across data types from cutting-edge sequencing platforms, we can help you tackle the challenging computational tasks of storing, analyzing, and interpreting genomic and transcriptomic data. Bridge Informatics’ bioinformaticians are trained bench biologists, so they understand the biological questions driving your computational analysis. From pipeline development and software engineering to deploying existing bioinformatics tools, Bridge Informatics can help you on every step of your research journey. Click here to schedule a free introductory call with a member of our team.

Jane Cook, Biochemist & Content Writer, Bridge Informatics

Jane Cook, the leading Content Writer for Bridge Informatics, has written over 100 articles on the latest topics and trends for the bioinformatics community. Jane’s broad and deep interdisciplinary molecular biology experience spans developing biochemistry assays to genomics. Prior to joining Bridge, Jane held research assistant roles in biochemistry research labs across a variety of therapeutic areas. While obtaining her B.A. in Biochemistry from Trinity College in Dublin, Ireland, Jane also studied journalism at New York University’s Arthur L. Carter Journalism Institute. As a native Texan, she embraces any challenge that comes her way. Jane hails from Dallas but returns to Ireland any and every chance she gets. If you’re interested in reaching out, please email [email protected] or [email protected].

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