COVID-19, Infection Inhibitors and Medicines

Hanai, T., MDPI AG, doi:10.20944/preprints202501.1042.v1

Jan 2025

In SIlico analysis of potential inhibitors and treatments for COVID-19 by analyzing the molecular interactions between the SARS-CoV-2 spike protein (S-RBD) and the human ACE-2 receptor. Author identifies tricarboxylic acids (citric acid, malic acid) and natural polyphenols (gallic acid, ferulic acid, glycyrrhizinic acid) as effective binding inhibitors, preventing viral entry. Common medications such as aspirin, ibuprofen, ritonavir, oseltamivir, and zanamivir also exhibited inhibitory effects. Modified versions of existing drugs that incorporate acidic groups may improve efficacy. Author emphasizes the rapid mutation of SARS-CoV-2 variants, reducing the efficacy of monoclonal antibodies, and underscores the potential of existing compounds to counteract COVID-19.

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Hanai et al., 14 Jan 2025, preprint, 1 author. Contact: hanai104@kf7.so-net.ne.jp.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

This Paper Miscellaneous All

COVID-19, Infection Inhibitors and Medicines

Toshihiko Hanai

doi:10.20944/preprints202501.1042.v1

The fast mutation of COVID-19 viruses still confuses us, and the mRNA vaccines do not inhibit the infection and may protect against the heavy disease. The infection mechanism is described with the protein-protein binding stereo structure; therefore, the infection strength of variants has been estimated from the protein-protein (S-RBD binding with ACE-2) interaction energy values calculated using a molecular mechanics program. The binding strength order was Alfa < Lambda < WT < FE.1 < XBB1.5 < EG.5 ≈ BQ.1 ≈ Alpha+E484K ≈ Omicron XBB.1.16 ≈ Epsilon, Iota < EG.5 < Delta plus ≈ Beta, Kappa B.1.621 ≈ KP.3 ≈ Kappa B.1.617.1 ≈ Delta B.1.517.2 < KP.2 < BA.2.86 ≈ JN.1 ≈ HV.1 ≈ BA.1 < BA.2. The mutation from acidic amino acid to basic amino acid strength the binding. The substitute size of amino acids causes the steric hindrance for the binding. The affinity level supports the infection strength. Various proposed infection inhibitors are quantitatively analyzed. TCA acids and natural polyphenols inhibit the binding of S-RBD to ACE-2. The cocktail dose of known medicines may enhance their performance. The inhibiting multiplication may be achieved using glycated compounds that bind glycoproteins and reduce glycoprotein activities.

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DOI record: { "DOI": "10.20944/preprints202501.1042.v1", "URL": "http://dx.doi.org/10.20944/preprints202501.1042.v1", "abstract": "The fast mutation of COVID-19 viruses still confuses us, and the mRNA vaccines do not inhibit the infection and may protect against the heavy disease. The infection mechanism is described with the protein-protein binding stereo structure; therefore, the infection strength of variants has been estimated from the protein-protein (S-RBD binding with ACE-2) interaction energy values calculated using a molecular mechanics program. The binding strength order was Alfa &lt; Lambda &lt; WT &lt; FE.1 &lt; XBB1.5 &lt; EG.5 ≈ BQ.1 ≈ Alpha+E484K ≈ Omicron XBB.1.16 ≈ Epsilon, Iota &lt; EG.5 &lt; Delta plus ≈ Beta, Kappa B.1.621 ≈ KP.3 ≈ Kappa B.1.617.1 ≈ Delta B.1.517.2 &lt; KP.2 &lt; BA.2.86 ≈ JN.1 ≈ HV.1 ≈ BA.1 &lt; BA.2. The mutation from acidic amino acid to basic amino acid strength the binding. The substitute size of amino acids causes the steric hindrance for the binding. The affinity level supports the infection strength. Various proposed infection inhibitors are quantitatively analyzed. TCA acids and natural polyphenols inhibit the binding of S-RBD to ACE-2. The cocktail dose of known medicines may enhance their performance. The inhibiting multiplication may be achieved using glycated compounds that bind glycoproteins and reduce glycoprotein activities.", "accepted": { "date-parts": [ [ 2025, 1, 13 ] ] }, "author": [ { "affiliation": [], "family": "Hanai", "given": "Toshihiko", "sequence": "first" } ], "container-title": [], "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2025, 1, 16 ] ], "date-time": "2025-01-16T02:07:55Z", "timestamp": 1736993275000 }, "deposited": { "date-parts": [ [ 2025, 1, 16 ] ], "date-time": "2025-01-16T02:09:54Z", "timestamp": 1736993394000 }, "group-title": "Medicine and Pharmacology", "indexed": { "date-parts": [ [ 2025, 1, 16 ] ], "date-time": "2025-01-16T05:40:35Z", "timestamp": 1737006035084, "version": "3.33.0" }, "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2025, 1, 14 ] ] }, "license": [ { "URL": "http://creativecommons.org/licenses/by/4.0", "content-version": "unspecified", "delay-in-days": 0, "start": { "date-parts": [ [ 2025, 1, 14 ] ], "date-time": "2025-01-14T00:00:00Z", "timestamp": 1736812800000 } } ], "member": "1968", "original-title": [], "posted": { "date-parts": [ [ 2025, 1, 14 ] ] }, "prefix": "10.20944", "published": { "date-parts": [ [ 2025, 1, 14 ] ] }, "publisher": "MDPI AG", "reference-count": 0, "references-count": 0, "relation": {}, "resource": { "primary": { "URL": "https://www.preprints.org/manuscript/202501.1042/v1" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "subtype": "preprint", "title": "COVID-19, Infection Inhibitors and Medicines", "type": "posted-content" }

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