Abstract
The recent outbreak caused by SARS-CoV-2 continues to threat and take many lives all over the world. The lack of an efficient pharmacological treatments are serious problems to be faced by scientists and medical staffs worldwide. In this work, an in silico approach based on the combination of molecular docking, dynamics simulations, and quantum biochemistry revealed that the synthetic peptides RcAlb-PepI, PepGAT, and PepKAA, strongly interact with the main protease (Mpro) a pivotal protein for SARS-CoV-2 replication. Although not binding to the proteolytic site of SARS-CoV-2 Mpro, RcAlb-PepI, PepGAT, and PepKAA interact with other protein domain and allosterically altered the protease topology. Indeed, such peptide-SARS-CoV-2 Mpro complexes provoked dramatic alterations in the three-dimensional structure of Mpro leading to area and volume shrinkage of the proteolytic site, which could affect the protease activity and thus the virus replication. Based on these findings, it is suggested that RcAlb-PepI, PepGAT, and PepKAA could interfere with SARS-CoV-2 Mpro role in vivo. Also, unlike other antiviral drugs, these peptides have no toxicity to human cells. This pioneering in silico investigation opens up opportunity for further in vivo research on these peptides, towards discovering new drugs and entirely new perspectives to treat COVID-19.
Communicated by Ramaswamy H. Sarma
Acknowledgements
The authors are also grateful to the support received from the National Center for High Performance Processing - Federal University of Ceara and Center for Permanent Education in Health Care-CEATS/School of Public Health of Ceara (ESP-CE). V.N.F. also acknowledges support from PRONEX FUNCAP/CNPq (PR2-0101-00006.01.00/15).
Disclosure statement
No potential conflict of interest was reported by the authors.
Author contributions
Conceptualization: Pedro F. N. Souza, Jackson L. Amaral. Francisco E. S. Lopes, and Jose T. A. Oliveira. Data curation: Pedro F. N. Souza, Jackson L. Amaral, Francisco E. S. Lopes, Cleverson D. T. Freitas, and Valder N. Freire. Formal analysis: Pedro F. N. Souza, Jackson L. Amaral, and Francisco E. S. Lopes. Funding acquisition: Jose T. A. Oliveira, Cleverson D. T. Freitas, and Valder N. Freire. Methodology: Jackson L. Amaral and Francisco E. S. Lopes. Resources: Jose T. A. Oliveira, Cleverson D. T. Freitas, and Valder N. Freire. Supervision: Pedro F. N. Souza. Writing–original draft: Pedro F. N. Souza, Jackson L. Amaral, Francisco E. S. Lopes, and Leonardo V. Abreu. Writing–review and editing: Pedro F. N. Souza, Jackson L. Amaral, Francisco E. S. Lopes, Leonardo V. Abreu, and Jose T. A. Oliveira.