Abstract

The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is considered the greatest challenge to the global health community of the century as it continues to expand. This has prompted immediate urgency to discover promising drug targets for the treatment of COVID-19. The SARS-CoV-2 viral proteases, 3-chymotrypsin-like protease (3CLpro) and papain-like cysteine protease (PLpro), have become the promising target to study due to their essential functions in spreading the virus by RNA transcription, translation, protein synthesis, processing and modification, virus replication, and infection of the host. As such, understanding of the structure and function of these two proteases is unavoidable as platforms for the development of inhibitors targeting this protein which further arrest the infection and spread of the virus. While the abundance of reports on the screening of natural compounds such as SARS-CoV-2 proteases inhibitors are available, the microorganisms-based compounds (peptides and non-peptides) remain less studied. Indeed, microorganisms-based compounds are also one of the potent antiviral candidates against COVID-19. Microbes, especially bacteria and fungi, are other resources to produce new drugs as well as nucleosides, nucleotides, and nucleic acids. Thus, we have compiled various reported literature in detail on the structures, functions of the SARS-CoV-2 proteases, and potential inhibitors from microbial sources as assistance to other researchers working with COVID-19. The compounds are also compared to HIV protease inhibitors which suggested the microorganisms-based compounds are advantageous as SARS-CoV2 proteases inhibitors. The information should serve as a platform for further development of COVID-19 drug design strategies.

Highlights

  • In late December 2019, a new strain of coronavirus resulted in the outbreak of a pneumonia-like illness in Wuhan, China and has become a life-threatening concern worldwide in the present time [1,2]

  • The compounds are compared to human immunodeficiency virus (HIV) protease inhibitors which suggested the microorganisms-based compounds are advantageous as SARS-CoV2 proteases inhibitors

  • It exists as a monomer in biological settings and has the USP fold, typical for the ubiquitin-specific proteases (USP) family in humans [67]

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Summary

Introduction

In late December 2019, a new strain of coronavirus resulted in the outbreak of a pneumonia-like illness in Wuhan, China and has become a life-threatening concern worldwide in the present time [1,2]. Microorganisms 2021, 9, x of 27 are zoonotic viruses that infect various vertebrates (pets, bats, livestock, poultry, and human), and among human, CoVs are responsible for respiratory, gastrointestinal, and neurological problems [9,10] They all contain very large RNA viruses’ genomes, with antigenic criteria [8]. Upon entry into the host cell, to their order from the N-terminus to the C-terminus of the ORF 1 polypeptides from two reach the replication stage, the CoV-2 genomic (+) sense ssRNA is used as mRNA to ultilargemately polyproteins, pp1a (4405 amino acids) and(nsp1–16), pp1ab (7096 aminoaccording acids) These produce 16 non-structural proteins numbered to theirtwo large polyproteins protease, known as thetwo. The development of fungi, cyanobacteria, and their metabolites and peptides as potential drugs for these two viral proteases are compiled

Structure of 3CLpro
The structurestructure of SARS-CoV-2
Functions of 3CLpro
Structure of PLpro
Cartoon
Functions of PLpro
Microorganisms as Sources of Inhibitors Targeting SARS-CoV2 Proteases
Binding Method
Microbial Natural Products as Potential Inhibitor of 3CLpro-CoV2
Microbial Natural Products as a Potential Inhibitor of PLpro-CoV2
Possibility of Inhibitors Targeting HIV Protease for SARS-CoV2 Proteases
Findings
Conclusions
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