Molecular-Level Targets for the Development of Therapies Against Coronavirus Diseases

Zhou, Q. A.; Granet, R.; Garner, L. V.

As research continues into the SARS-CoV-2 infection process, many viral and human proteins and other biomolecules have been identified as potential drug targets for treating this and other coronavirus infections. The most therapeutically promising of these include: (1) proteins involved in SARS-CoV-2 entry into host cells, such as the viral spike (S) protein, the human angiotensin-converting enzyme 2 (ACE2), and human proteases needed to cleave the S protein in preparation for cell membrane fusion;(2) nucleic acid–related enzymes involved in viral RNA replication such as the viral RNA-dependent RNA polymerase (RdRp) and helicase;(3) viral proteases 3-Chymotrypsin-like protease (3CLPro) and Papain-like protease (PLpro), which autocatalytically cleave the polyprotein translated from viral RNA;and (4) other intracellular human proteins the virus uses for replication and extracellular proteins the virus regulates to cause inflammation, blood coagulation and other problems associated with infection. In this chapter, we discuss these promising target proteins in terms of their structure, function, and possible chemical or biological modulators.