Computational drug repurposing strategy predicted peptide-based drugs that can potentially inhibit the interaction of SARS-CoV-2 spike protein with its target (humanACE2)

Abstract

Drug repurposing for COVID-19 has several potential benefits including shorter development time, reduced costs and regulatory support for faster time to market for treatment that can alleviate the current pandemic. The current study used molecular docking, molecular dynamics and protein-protein interaction simulations to predict drugs from the Drug Bank that can bind to the SARS-CoV-2 spike protein interacting surface on the human angiotensin-converting enzyme 2 (hACE2) receptor. The study predicted a number of peptide-based drugs, including Sar9 Met (O2)11-Substance P and BV2, that might bind sufficiently to the hACE2 receptor to modulate the protein-protein interaction required for infection by the SARS-CoV-2 virus. Such drugs could be validated in vitro or in vivo as potential inhibitors of the interaction of SARS-CoV-2 spike protein with the human angiotensin-converting enzyme 2 (hACE2) in the airway. Exploration of the proposed and current pharmacological indications of the peptide drugs predicted as potential inhibitors of the interaction between the spike protein and hACE2 receptor revealed that some of the predicted peptide drugs have been investigated for the treatment of acute respiratory distress syndrome (ARDS), viral infection, inflammation and angioedema, and to stimulate the immune system, and potentiate antiviral agents against influenza virus. Furthermore, these predicted drug hits may be used as a basis to design new peptide or peptidomimetic drugs with better affinity and specificity for the hACE2 receptor that may prevent interaction between SARS-CoV-2 spike protein and hACE2 that is prerequisite to the infection by the SARS-CoV-2 virus.

A Comprehensive Review of Drug Repurposing Strategies against Known Drug Targets of COVID-19

“…Similarly, 15 drugs-quinapril, sofosbuvir, amphotericin B, baloxavir marboxil, fosinopril, danoprevir, clarithromycin, atrovastatin, telmisartan, sulfamethoxazole, virginiamycin, micafungin, tunicamycin, caspofungin, and fidaxomicin-which are FDA-approved, were established as SARS-CoV-2 protein inhibitors in an approach confirmed by docking protocol. They could be explored as drug candidates against COVID-19 in the future and be repurposed against SARS-COV-2 [64].…”

Tripeptides from Allium subhirsitum L. extracts: Pharmacokinetics properties, toxicity prediction and in silico study against SARS-CoV-2 enzymes and pro-inflammatory proteins

“…It has been also demonstrated that peptides retrieved from the Antiviral Peptides Database (AVPdb; ( 68)) can interact with several target proteins involved in the SARS-CoV2 virus life cycle like the receptor-binding domain of spike protein and hACE2 receptor (42). Interestingly, two peptides namely Sar9 Met (O2)11-Substance P and Sar9 Met (O2)11-Substance P were able to bind to the hACE2 receptor which modulate the interaction of viral particles with its host cell receptors (47).…”

A Perspective on Nanotechnology and COVID-19 Vaccine Research and Production in South Africa

“…Overall, whole-genome sequencing projects and the rise of bioinformatics have triggered the birth of a new era of vaccine research and development, leading to a new generation of vaccines designed by deciphering the information provided by genome sequences and using it to better understand the host–pathogen interactions [ 46 ]. Riding on the capacity developed, as well as the gains from the use of bioinformatics to develop insights into the dynamics of other infectious diseases, means that South African scientists are poised to continue applying -omics informatics approaches to advance the prevention and treatment of diseases, including COVID-19 [ 46 , 47 ].…”