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Structure-based drug designing and immunoinformatics approach for SARS-CoV-2.
Sci Adv. 2020 07; 6(28):eabb8097.SA

Abstract

The prevalence of respiratory illness caused by the novel SARS-CoV-2 virus associated with multiple organ failures is spreading rapidly because of its contagious human-to-human transmission and inadequate globalhealth care systems. Pharmaceutical repurposing, an effective drug development technique using existing drugs, could shorten development time and reduce costs compared to those of de novo drug discovery. We carried out virtual screening of antiviral compounds targeting the spike glycoprotein (S), main protease (Mpro), and the SARS-CoV-2 receptor binding domain (RBD)-angiotensin-converting enzyme 2 (ACE2) complex of SARS-CoV-2. PC786, an antiviral polymerase inhibitor, showed enhanced binding affinity to all the targets. Furthermore, the postfusion conformation of the trimeric S protein RBD with ACE2 revealed conformational changes associated with PC786 drug binding. Exploiting immunoinformatics to identify T cell and B cell epitopes could guide future experimental studies with a higher probability of discovering appropriate vaccine candidates with fewer experiments and higher reliability.

Authors+Show Affiliations

Condensed Matter Theory Group, Materials Theory Division, Department of Physics and Astronomy, Uppsala University, Box 516, SE-751 20 Uppsala, Sweden.Department of Theoretical Chemistry and Biology, Royal Institute of Technology (KTH), AlbaNova University Center, 106 91 Stockholm, Sweden.School of Biotechnology, KIIT University, Bhubaneswar 751024, India.School of Biotechnology, KIIT University, Bhubaneswar 751024, India.Condensed Matter Theory Group, Materials Theory Division, Department of Physics and Astronomy, Uppsala University, Box 516, SE-751 20 Uppsala, Sweden.Syddansk Universitet, Alsion 2, DK-6400 Sønderborg, Denmark.Mads Clausen Institute, NanoSYD, University of Southern Denmark, Alsion 2, DK-6400 Sønderborg, Denmark.School of Biotechnology, KIIT University, Bhubaneswar 751024, India.Condensed Matter Theory Group, Materials Theory Division, Department of Physics and Astronomy, Uppsala University, Box 516, SE-751 20 Uppsala, Sweden. Applied Materials Physics, Department of Materials Science and Engineering, Royal Institute of Technology (KTH), SE-100 44 Stockholm, Sweden.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32691011

Citation

Panda, Pritam Kumar, et al. "Structure-based Drug Designing and Immunoinformatics Approach for SARS-CoV-2." Science Advances, vol. 6, no. 28, 2020, pp. eabb8097.
Panda PK, Arul MN, Patel P, et al. Structure-based drug designing and immunoinformatics approach for SARS-CoV-2. Sci Adv. 2020;6(28):eabb8097.
Panda, P. K., Arul, M. N., Patel, P., Verma, S. K., Luo, W., Rubahn, H. G., Mishra, Y. K., Suar, M., & Ahuja, R. (2020). Structure-based drug designing and immunoinformatics approach for SARS-CoV-2. Science Advances, 6(28), eabb8097. https://doi.org/10.1126/sciadv.abb8097
Panda PK, et al. Structure-based Drug Designing and Immunoinformatics Approach for SARS-CoV-2. Sci Adv. 2020;6(28):eabb8097. PubMed PMID: 32691011.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structure-based drug designing and immunoinformatics approach for SARS-CoV-2. AU - Panda,Pritam Kumar, AU - Arul,Murugan Natarajan, AU - Patel,Paritosh, AU - Verma,Suresh K, AU - Luo,Wei, AU - Rubahn,Horst-Günter, AU - Mishra,Yogendra Kumar, AU - Suar,Mrutyunjay, AU - Ahuja,Rajeev, Y1 - 2020/07/10/ PY - 2020/03/19/received PY - 2020/05/27/accepted PY - 2020/7/22/entrez PY - 2020/7/22/pubmed PY - 2020/7/31/medline SP - eabb8097 EP - eabb8097 JF - Science advances JO - Sci Adv VL - 6 IS - 28 N2 - The prevalence of respiratory illness caused by the novel SARS-CoV-2 virus associated with multiple organ failures is spreading rapidly because of its contagious human-to-human transmission and inadequate globalhealth care systems. Pharmaceutical repurposing, an effective drug development technique using existing drugs, could shorten development time and reduce costs compared to those of de novo drug discovery. We carried out virtual screening of antiviral compounds targeting the spike glycoprotein (S), main protease (Mpro), and the SARS-CoV-2 receptor binding domain (RBD)-angiotensin-converting enzyme 2 (ACE2) complex of SARS-CoV-2. PC786, an antiviral polymerase inhibitor, showed enhanced binding affinity to all the targets. Furthermore, the postfusion conformation of the trimeric S protein RBD with ACE2 revealed conformational changes associated with PC786 drug binding. Exploiting immunoinformatics to identify T cell and B cell epitopes could guide future experimental studies with a higher probability of discovering appropriate vaccine candidates with fewer experiments and higher reliability. SN - 2375-2548 UR - https://www.unboundmedicine.com/medline/citation/32691011/Structure_based_drug_designing_and_immunoinformatics_approach_for_SARS_CoV_2_ L2 - https://doi.org/10.1126/sciadv.abb8097 DB - PRIME DP - Unbound Medicine ER -