Title:Recent Advances Towards Drug Design Targeting the Protease of 2019 Novel Coronavirus (2019-nCoV)
Volume: 28
Issue: 22
Author(s): Sehrish Bano, Abdul Hameed, Mariya Al-Rashida, Shafia Iftikhar and Jamshed Iqbal*
Affiliation:
- Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad,Pakistan
Keywords:
coronavirus, protease-like 3-chymotrypsin (3CLpro), protease-like papain (PLpro), remdesivir, SARSCoV-
2, non-structural proteins, ATP.
Abstract:
Background: The 2019 novel coronavirus (2019-nCoV), also known as coronavirus
2 (SARS-CoV-2) acute respiratory syndrome has recently emerged and continued
to spread rapidly with high mortality and morbidity rates. Currently, no efficacious therapy
is available to relieve coronavirus infections. As new drug design and development
takes time, there is a possibility offindingan effective treatment from existing antiviral
agents.
Objective: The aim of this study is to find out the relationship between thepossible drug
targets and themechanism of action of antiviral drugs. This review discusses the efforts
indevelopingdrug from known or new molecules.
Methods: Viruses usually have two structural integrities, proteins and nucleic acids, both
of which can be possible drug targets. Herein, we systemically discuss the structural-functional
relationships of the spike, 3-chymotrypsin-like protease (3CLpro), papain like protease
(PLpro) and RNA-dependent RNA polymerase (RdRp), as these are prominent
structural features of thecoronavirus. Certain antiviral drugs such as Remdesivir are
RNA-dependent RNA polymerase inhibitorswiththe ability to terminate RNA replication
by inhibiting ATP.
Results: It is reported that ATP is involved in synthesis of coronavirus non-structural proteins
from 3CLpro and PLpro. Similarly, mechanisms of action of many other antiviral
agents havebeen discussed in this review. It will provide new insights into the mechanism
of inhibition, and let us develop new therapeutic antiviral approaches against novel
SARS-CoV-2 coronavirus.
Conclusion: In conclusion, this review summarizes recent progress in developing protease
inhibitors for SARS-CoV-2.
