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Review

Role of Structural and Non-Structural Proteins and Therapeutic Targets of SARS-CoV-2 for COVID-19

1
Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Rishikesh 249203, India
2
Department of Zoology, Shivaji College, University of Delhi, Delhi 110027, India
3
Department of Medical Oncology & Hematology, All India Institute of Medical Sciences (AIIMS), Rishikesh 249203, India
4
Molecular Biology & Proteomics Laboratory, Department of Biotechnology, Indian Institute of Technology (IIT), Roorkee 247667, India
5
Uttaranchal Institute of Pharmaceutical Sciences, Dehradun 248007, India
6
Department of Biochemistry, U.P. Pt. Deen Dayal Upadhyaya Veterinary Science University, Mathura 281001, India
7
Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh 249203, India
*
Author to whom correspondence should be addressed.
These authors contributed to this work equally.
Academic Editor: Hiroshi Miyamoto
Cells 2021, 10(4), 821; https://doi.org/10.3390/cells10040821
Received: 25 February 2021 / Revised: 31 March 2021 / Accepted: 1 April 2021 / Published: 6 April 2021
Coronavirus belongs to the family of Coronaviridae, comprising single-stranded, positive-sense RNA genome (+ ssRNA) of around 26 to 32 kilobases, and has been known to cause infection to a myriad of mammalian hosts, such as humans, cats, bats, civets, dogs, and camels with varied consequences in terms of death and debilitation. Strikingly, novel coronavirus (2019-nCoV), later renamed as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and found to be the causative agent of coronavirus disease-19 (COVID-19), shows 88% of sequence identity with bat-SL-CoVZC45 and bat-SL-CoVZXC21, 79% with SARS-CoV and 50% with MERS-CoV, respectively. Despite key amino acid residual variability, there is an incredible structural similarity between the receptor binding domain (RBD) of spike protein (S) of SARS-CoV-2 and SARS-CoV. During infection, spike protein of SARS-CoV-2 compared to SARS-CoV displays 10–20 times greater affinity for its cognate host cell receptor, angiotensin-converting enzyme 2 (ACE2), leading proteolytic cleavage of S protein by transmembrane protease serine 2 (TMPRSS2). Following cellular entry, the ORF-1a and ORF-1ab, located downstream to 5′ end of + ssRNA genome, undergo translation, thereby forming two large polyproteins, pp1a and pp1ab. These polyproteins, following protease-induced cleavage and molecular assembly, form functional viral RNA polymerase, also referred to as replicase. Thereafter, uninterrupted orchestrated replication-transcription molecular events lead to the synthesis of multiple nested sets of subgenomic mRNAs (sgRNAs), which are finally translated to several structural and accessory proteins participating in structure formation and various molecular functions of virus, respectively. These multiple structural proteins assemble and encapsulate genomic RNA (gRNA), resulting in numerous viral progenies, which eventually exit the host cell, and spread infection to rest of the body. In this review, we primarily focus on genomic organization, structural and non-structural protein components, and potential prospective molecular targets for development of therapeutic drugs, convalescent plasm therapy, and a myriad of potential vaccines to tackle SARS-CoV-2 infection. View Full-Text
Keywords: coronavirus; structural proteins; Angiotensin converting enzyme 2; Coronavirus disease-19; SARS-CoV-2 coronavirus; structural proteins; Angiotensin converting enzyme 2; Coronavirus disease-19; SARS-CoV-2
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MDPI and ACS Style

Yadav, R.; Chaudhary, J.K.; Jain, N.; Chaudhary, P.K.; Khanra, S.; Dhamija, P.; Sharma, A.; Kumar, A.; Handu, S. Role of Structural and Non-Structural Proteins and Therapeutic Targets of SARS-CoV-2 for COVID-19. Cells 2021, 10, 821. https://doi.org/10.3390/cells10040821

AMA Style

Yadav R, Chaudhary JK, Jain N, Chaudhary PK, Khanra S, Dhamija P, Sharma A, Kumar A, Handu S. Role of Structural and Non-Structural Proteins and Therapeutic Targets of SARS-CoV-2 for COVID-19. Cells. 2021; 10(4):821. https://doi.org/10.3390/cells10040821

Chicago/Turabian Style

Yadav, Rohitash, Jitendra K. Chaudhary, Neeraj Jain, Pankaj K. Chaudhary, Supriya Khanra, Puneet Dhamija, Ambika Sharma, Ashish Kumar, and Shailendra Handu. 2021. "Role of Structural and Non-Structural Proteins and Therapeutic Targets of SARS-CoV-2 for COVID-19" Cells 10, no. 4: 821. https://doi.org/10.3390/cells10040821

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