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Identification of potential Indonesian marine invertebrate bioactive compounds as TMPRSS2 and SARS-CoV-2 Omicron spike protein inhibitors through computational screening.

ABSTRACT: The coronavirus pandemic led to the announcement of a worldwide health emergency. The SARS-CoV-2 Omicron variant, which swiftly spread worldwide, has fueled existing challenges. Appropriate medication is necessary to avoid severe SARS-CoV-2 disease. The human TMPRSS2 and SARS-CoV-2 Omicron spike protein, which are required for viral entry into the host phase, were identified as the target proteins through computational screening. Structure-based virtual screening; molecular docking; absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis; and molecular dynamics simulation were the methods applied for TMPRSS2 and spike protein inhibitors. Bioactive marine invertebrates from Indonesia were employed as test ligands. Camostat and nafamostat (co-crystal) were utilized as reference ligands against TMPRSS2, whereas mefloquine was used as a reference ligand against spike protein. Following a molecular docking and dynamics simulation, we found that acanthomanzamine C has remarkable effectiveness against TMPRSS2 and spike protein. Compared to camostat (-8.25 kcal/mol), nafamostat (-6.52 kcal/mol), and mefloquine (-6.34 kcal/mol), acanthomanzamine C binds to TMPRSS2 and spike protein with binding energies of -9.75 kcal/mol and -9.19 kcal/mol, respectively. Furthermore, slight variances in the MD simulation demonstrated consistent binding to TMPRSS2 and spike protein after the initial 50 ns. These results are highly valuable in the search for a treatment for SARS-CoV-2 infection.

SUBMITTER: Rizka Nurcahyaningtyas H

PROVIDER: S-EPMC10186851 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Identification of potential Indonesian marine invertebrate bioactive compounds as TMPRSS2 and SARS-CoV-2 Omicron spike protein inhibitors through computational screening.

Rizka Nurcahyaningtyas Haviani H Irene Alfrina A Tri Wibowo Joko J Yunovilsa Putra Masteria M Yanuar Arry A

Arabian journal of chemistry 20230516 9

The coronavirus pandemic led to the announcement of a worldwide health emergency. The SARS-CoV-2 Omicron variant, which swiftly spread worldwide, has fueled existing challenges. Appropriate medication is necessary to avoid severe SARS-CoV-2 disease. The human TMPRSS2 and SARS-CoV-2 Omicron spike protein, which are required for viral entry into the host phase, were identified as the target proteins through computational screening. Structure-based virtual screening; molecular docking; absorption, ...[more]

PMID: 37234226

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Project description:Omicron is an emerging SARS-CoV-2 variant, evolved from the Indian delta variant B.1.617.2, which is currently infecting worldwide. The spike glycoprotein, an important molecule in the pathogenesis and transmissions of SARS-CoV-2 variants, especially omicron B.1.1.529, shows 37 mutations distributed over the trimeric protein domains. Notably, fifteen of these mutations reside in the receptor-binding domain of the spike glycoprotein, which may alter transmissibility and infectivity. Additionally, the omicron spike evades neutralization more efficiently than the delta spike. Most of the therapeutic antibodies are ineffective against the omicron variant, and double immunization with BioNTech-Pfizer (BNT162b2) might not adequately protect against severe disease induced by omicron B.1.1.529. So far, no efficient antiviral drugs are available against omicron. The present study identified the promising inhibitors from seaweed's bioactive compounds to inhibit the omicron variant B.1.1.529. We have also compared the seaweed's compounds with the standard drugs ceftriaxone and cefuroxime, which were suggested as beneficial antiviral drugs in COVID-19 treatment. Our molecular docking analysis revealed that caffeic acid hexoside (-6.4 kcal/mol; RMSD = 2.382 Å) and phloretin (-6.3 kcal/mol; RMSD = 0.061 Å) from Sargassum wightii (S. wightii) showed the inhibitory effect against the crucial residues ASN417, SER496, TYR501, and HIS505, which are supported for the inviolable omicron and angiotensin-converting enzyme II (ACE2) receptor interaction. Cholestan-3-ol, 2-methylene-, (3beta, 5 alpha) (CMBA) (-6.0 kcal/mol; RMSD = 3.074 Å) from Corallina officinalis (C. officinalis) manifested the strong inhibitory effect against the omicron RBD mutated residues LEU452 and ALA484, was magnificently observed as the essential residues in Indian delta variant B.1.617.2 previously. The standard drugs (ceftriaxone and cefuroxime) showed no or less inhibitory effect against RBD of omicron B.1.1.529. The present study also emphasized the pharmacological properties of the considered chemical compounds. The results could be used to develop potent seaweed-based antiviral drugs and/or dietary supplements to treat omicron B.1.1529-infected patients.

Project description:Nowadays, endophytic fungi represent a rich source of biological active compounds. In the current study, twelve endophytic fungal species were isolated from Avicennia marina leaves. From the isolates, Aspergillus niger, Penicillium rubens and Alternaria alternata recorded the highest isolation frequency (80%), relative density (12.5%) and antimicrobial activity. The antimicrobial and anticancer activities of P. rubens were more effective than those of A. niger and A. alternata; therefore, its identification was confirmed via the ITS rRNA gene. Filtrate extracts of P. rubens, A. alternata and A. niger were analyzed using GC-MS and showed different detected constituents, such as acetic acid ethyl ester, N-(4,6-Dimethyl-2-pyrimidinyl)-4-(4-nitrobenzylideneamino) benzenesulfonamide, 1,2-benzenedicarboxylic acid, hexadecanoic acid and octadecanoic acid. Filtrate extract of P. rubens exhibited the presence of more compounds than A. alternata and A. niger. Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and Aspergillus fumigatus were more inhibited by P. rubens extract than A. alternata or A. niger, with inhibition zones of 27.2 mm, 22.21 mm, 26.26 mm, 27.33 mm, 28.25 mm and 8.5 mm, respectively. We observed negligible cytotoxicity of P. rubens extract against normal cells of human lung fibroblasts (WI-38 cell line), unlike A. alternata and A. niger extracts. Proliferation of prostate cancer (PC-3) was inhibited using P. rubens extract, exhibiting mortality levels of 75.91% and 76.2% at 200 µg/mL and 400 µg/mL of the extract. Molecular docking studies against the crystal structures of C. albicans (6TZ6) and the cryo-EM structure of B. subtilis (7CKQ) showed significant interactions with benzenedicarboxylic acid and N-(4,6-dimethyl-2-pyrimidinyl)-4-(4-nitrobenzylideneamino) benzenesulfonamide as a constituent of P. rubens extract. N-(4,6-dimethyl-2-pyrimidinyl)-4-(4-nitrobenzylideneamino) benzenesulfonamide had the highest scores of −6.04905 kcal/mol and −6.590 kcal/mol towards (6tz6) and (7CKQ), respectively.

Dataset Information

Identification of potential Indonesian marine invertebrate bioactive compounds as TMPRSS2 and SARS-CoV-2 Omicron spike protein inhibitors through computational screening.

Publications

Identification of potential Indonesian marine invertebrate bioactive compounds as TMPRSS2 and SARS-CoV-2 Omicron spike protein inhibitors through computational screening.

Similar Datasets

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