16 Mar Corona: A Possibility to Block Cell Entry?

MedicalResearch.com Interview with:

Dr. Sibaji Sarkar

Sibaji Sarkar, Ph.D.
Adj. Professor
Quincy College, Quincy, Boston MA
MBC College, Wellesley MA
RC College, Boston, MA 

MedicalResearch.com: What is the background for this study?

Response: COVID-19 infection is spreading and nothing is out there now to stop it. Hopefully, vaccines will be made and will be useful but that may take months if not a year. Researchers are also testing the use of other anti-viral drugs. COVID-19 uses (angiotensin converting enzyme receptor 2) ACE2 on capillary membranes of lungs to attach and then enter by endocytosis. ACE and ACE2 are two different types of receptors. ACE inhibitors are regularly in use as blood pressure lowering drugs. Unfortunately, ACE inhibitors have very les affinity for ACE2. Theoretically, if COVID-19 and any ACE2 inhibitor share similar binding site on ACE2 or at least bind in close proximity, assuming the virus is a big particle, it should fully or partially block viral entry. That will reduce or delay disease progression.

Some years ago, researchers identified some peptide inhibitors which selectively bind and inhibit ACE2. Another study identified small molecule inhibitors which block SARS-Cov entry either by inhibiting ACE2, or by inhibiting the protease cathepsin L , which process the virus protein or by blocking the fusion of the virus with the membrane.

A study has shown before that cathepsin L inhibition prevents SARS-CoV entry. These and other related inhibitors if available, should be immediately tested whether they can fully or partially block COVID- 19 entry to lungs. If successful, this will provide another tool to combat Corona Virus. It is time that we start thinking about it and working on it. 

References.

1. Huang L, Sexton DL, Skogerson K, Devlin M, Smith R, Sanyal I, Parry T, Kent R, Enright J, Wu Q-L, Conley G, DeOliveira D, Morganelli L, Ducar M, Wescott CR, and Ladner RC. Novel Peptide Inhibitors of Angiotensin-converting Enzyme 2. J. Biol. Chem. 278, 15532-15540, 2003.
2. Adedeji AO, Severson W, Jonsson C, Singh K, Weiss SR, Sarafianosa SG. Novel Inhibitors of Severe Acute Respiratory Syndrome Coronavirus Entry That Act by Three Distinct Mechanisms. J. Virol. 87, 8017-8028, 2013.
3. Simmons G, Gosalia DN, Rennekamp AJ, Reeves JD, Diamond SL, and Bates P. Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry Proc. Natl. Acad. Sci, USA. 102, 11876–11881, 2005. 

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Last Updated on March 16, 2020 by Marie Benz MD FAAD