Molecular Docking and In-Silico Analysis of Natural Biomolecules against Dengue, Ebola, Zika, SARS-CoV-2 Variants of Concern and Monkeypox Virus

Abstract

The emergence and rapid evolution of human pathogenic viruses, combined with the difficulties in developing effective vaccines, underline the need to develop innovative broad-spectrum antiviral therapeutic agents. The present study aims to determine the in silico antiviral potential of six bacterial antimicrobial peptides (AMPs), two phytochemicals (silvestrol, andrographolide), and two bacterial secondary metabolites (lyngbyabellin A, hapalindole H) against dengue virus, Zika virus, Ebola virus, the major variants of SARS-CoV-2 and monkeypox virus. The comparison of docking scores obtained with natural biomolecules was performed with specific neutralizing antibodies (positive controls for ClusPro) and antiviral drugs (negative controls for Autodock Vina). Glycocin F was the only natural biomolecule tested to show high binding energies to all viral surface proteins and the corresponding viral cell receptors. Lactococcin G and plantaricin ASM1 also achieved high docking scores with all viral surface proteins and most corresponding cell surface receptors. Silvestrol, andrographolide, hapalindole H, and lyngbyabellin A showed variable docking scores depending on the viral surface proteins and cell receptors tested. Three glycocin F mutants with amino acid modifications showed an increase in their docking energy to the spike proteins of SARS-CoV-2 B.1.617.2 Indian variant, and of the SARS-CoV-2 P.1 Japan/Brazil variant, and the dengue DENV envelope protein. All mutant AMPs indicated a frequent occurrence of valine and proline amino acid rotamers. AMPs and glycocin F in particular are the most promising biomolecules for the development of broad-spectrum antiviral treatments targeting the attachment and entry of viruses into their target cell.

Structural, Hirshfeld surface and molecular docking studies of a new organotin(IV)-phosphoric triamide complex and an amidophosphoric acid ester proposed as possible SARS-CoV-2 and Monkeypox inhibitors

“…These negative values point to a possible disruption of the protein activity suggesting the compounds 1 and 2 could be potential inhibitors of Monkeypox. However, the binding energy affinity scores between 4QWO and Monkeypox drugs such as Tecovirimat (−9.6 kcal/mol for 4QWO) and Brincidofovir (−9.8 kcal/mol) [ 54 ] are slightly more negative.…”

Computational Purposing Phytochemicals against Cysteine Protease of Monkeypox Virus: An In-silico Approach

“…20 A natural biomolecule Glycocin F showed the highest binding with MPXV. 12 High docking scores were also attained by lactococcin G and plantaricin ASM1 with the majority of related cell surface receptors and viral surface proteins. Study with phytochemicals is missing in literature; however, our team has published several reviews and editorial paper on monkeypox outbreak with promising insight into future perspectives.…”

“…So, the scientists are exploring something new and natural remedies including of medicinal herbs, plant metabolites and phytochemicals for these viruses that can be effective and safe alternative for these drugs as found useful against various important emerging and re-emerging pathogens. [9][10][11][12] In addition, about 50 single nucleotide polymorphisms (SNPs) were discovered in the 2022 MPXV genome that were not present in the 2018-2019 MPXV strains that were circulating. This adds to the seriousness of the ongoing global pandemic and that MPXV is accelerating its progression.…”

“…Phytochemicals and other medications have been projected to be effective against SARS-CoV-2, Ebola, and Nipah virus in numerous in silico and pharmacoinformatics-based investigations. 10,12,21 In the present study, our team has explored various compounds of well-known Indian medicinal plant Allophylus serratus for its potential to spread and prevent monkeypox disease. This drug is known in Ayurveda for its anti-viral and anti-inflammatory properties.…”

In-silico investigation on the discovery of synthesized nucleoside-based antivirals against monkeypox and SARS-CoV-2 Virus

“…Hydrogen bonds, hydrophobic bonds, and electrostatic interactions were looked at for each molecule. The stronger docking of each ligand molecule with its respective receptor was determined by the higher docking energy score [24]. H-bonding and hydrophobic bonding are the key determinants of docking values because they play a significant role in the creation of structurally based medications [51].…”