In Silico Screening of Bioactive Compounds of Representative Seaweeds to Inhibit SARS-CoV-2 ACE2-Bound Omicron B.1.1.529 Spike Protein Trimer

Abstract

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.

Evolutionary progression of collective mutations in Omicron sub-lineages towards efficient RBD-hACE2: Allosteric communications between and within viral and human proteins

“…Tyr508 is located just outside the RBM region at the N-terminus end of the β7. Tyr508 is involved in the RBD-hACE2 interaction [113] , [114] , binding and interaction with camel nanobodies for RBD neutralization [115] , standard drugs [116] , [117] , inhibitory peptides [118] , metal complexes [119] and natural inhibitory compounds [120] . Val510 binds a number of natural bioactive compounds with potential antiviral properties [116] , [121] , [122] .…”

Lucidenic acid A inhibits the binding of hACE2 receptor with spike protein to prevent SARS-CoV-2 invasion

“…The SARS-CoV-2 infection cycle begins with viral recognition and binding to the surface receptors, which subsequently induces the viral endocytosis into host cell. It undergoes conformational changes and proteolytic changes of the S protein, then fuses with the cell membrane, transcription and replication of viral RNA by using endogenous organelles to translate its replicase ( Bharathi et al, 2022 ). Genomic RNA (gRNA), as the translation template of polymeric protein pp1a and pp1ab, is cleaved to form non structural proteins (NSPs) and promote the formation of double membrane vesicles in cell membrane.…”

Evolutionary progression of collective mutations in Omicron sub-lineages towards efficient RBD-hACE2: allosteric communications between and within viral and human proteins

“…Tyr508 is located just outside the RBM region at the N-terminus end of the β7. Tyr508 is involved in the RBD-hACE2 interaction [113, 114], binding and interaction with camel nanobodies for RBD neutralization [115], standard drugs [116, 117], inhibitory peptides [118], metal complexes [119] and natural inhibitory compounds [120]. Val510 binds a number of natural bioactive compounds with potential antiviral properties [116, 121, 122].…”