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COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles' heel conserved region to minimize probability of escape mutations and drug resistance.
Comput Biol Med. 2020 06; 121:103749.CB

Abstract

This paper continues a recent study of the spike protein sequence of the COVID-19 virus (SARS-CoV-2). It is also in part an introductory review to relevant computational techniques for tackling viral threats, using COVID-19 as an example. Q-UEL tools for facilitating access to knowledge and bioinformatics tools were again used for efficiency, but the focus in this paper is even more on the virus. Subsequence KRSFIEDLLFNKV of the S2' spike glycoprotein proteolytic cleavage site continues to appear important. Here it is shown to be recognizable in the common cold coronaviruses, avian coronaviruses and possibly as traces in the nidoviruses of reptiles and fish. Its function or functions thus seem important to the coronaviruses. It might represent SARS-CoV-2 Achilles' heel, less likely to acquire resistance by mutation, as has happened in some early SARS vaccine studies discussed in the previous paper. Preliminary conformational analysis of the receptor (ACE2) binding site of the spike protein is carried out suggesting that while it is somewhat conserved, it appears to be more variable than KRSFIEDLLFNKV. However compounds like emodin that inhibit SARS entry, apparently by binding ACE2, might also have functions at several different human protein binding sites. The enzyme 11β-hydroxysteroid dehydrogenase type 1 is again argued to be a convenient model pharmacophore perhaps representing an ensemble of targets, and it is noted that it occurs both in lung and alimentary tract. Perhaps it benefits the virus to block an inflammatory response by inhibiting the dehydrogenase, but a fairly complex web involves several possible targets.

Authors+Show Affiliations

Ingine Inc. Cleveland Ohio USA, The Dirac Foundation, Oxfordshire, UK. Electronic address: barryrobson@ingine.com.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32568687

Citation

Robson, B. "COVID-19 Coronavirus Spike Protein Analysis for Synthetic Vaccines, a Peptidomimetic Antagonist, and Therapeutic Drugs, and Analysis of a Proposed Achilles' Heel Conserved Region to Minimize Probability of Escape Mutations and Drug Resistance." Computers in Biology and Medicine, vol. 121, 2020, p. 103749.
Robson B. COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles' heel conserved region to minimize probability of escape mutations and drug resistance. Comput Biol Med. 2020;121:103749.
Robson, B. (2020). COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles' heel conserved region to minimize probability of escape mutations and drug resistance. Computers in Biology and Medicine, 121, 103749. https://doi.org/10.1016/j.compbiomed.2020.103749
Robson B. COVID-19 Coronavirus Spike Protein Analysis for Synthetic Vaccines, a Peptidomimetic Antagonist, and Therapeutic Drugs, and Analysis of a Proposed Achilles' Heel Conserved Region to Minimize Probability of Escape Mutations and Drug Resistance. Comput Biol Med. 2020;121:103749. PubMed PMID: 32568687.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles' heel conserved region to minimize probability of escape mutations and drug resistance. A1 - Robson,B, Y1 - 2020/04/11/ PY - 2020/03/15/received PY - 2020/04/03/revised PY - 2020/04/03/accepted PY - 2020/6/23/entrez PY - 2020/6/23/pubmed PY - 2020/7/4/medline KW - 2019-nCoV KW - Bionformatics KW - COVID-19 KW - Coronavirus KW - Peptidomimetic KW - Q-UEL language KW - Retroinverso KW - SARS-CoV-2 KW - Synthetic vaccine KW - Wuhan seafood market coronavirus SP - 103749 EP - 103749 JF - Computers in biology and medicine JO - Comput Biol Med VL - 121 N2 - This paper continues a recent study of the spike protein sequence of the COVID-19 virus (SARS-CoV-2). It is also in part an introductory review to relevant computational techniques for tackling viral threats, using COVID-19 as an example. Q-UEL tools for facilitating access to knowledge and bioinformatics tools were again used for efficiency, but the focus in this paper is even more on the virus. Subsequence KRSFIEDLLFNKV of the S2' spike glycoprotein proteolytic cleavage site continues to appear important. Here it is shown to be recognizable in the common cold coronaviruses, avian coronaviruses and possibly as traces in the nidoviruses of reptiles and fish. Its function or functions thus seem important to the coronaviruses. It might represent SARS-CoV-2 Achilles' heel, less likely to acquire resistance by mutation, as has happened in some early SARS vaccine studies discussed in the previous paper. Preliminary conformational analysis of the receptor (ACE2) binding site of the spike protein is carried out suggesting that while it is somewhat conserved, it appears to be more variable than KRSFIEDLLFNKV. However compounds like emodin that inhibit SARS entry, apparently by binding ACE2, might also have functions at several different human protein binding sites. The enzyme 11β-hydroxysteroid dehydrogenase type 1 is again argued to be a convenient model pharmacophore perhaps representing an ensemble of targets, and it is noted that it occurs both in lung and alimentary tract. Perhaps it benefits the virus to block an inflammatory response by inhibiting the dehydrogenase, but a fairly complex web involves several possible targets. SN - 1879-0534 UR - https://www.unboundmedicine.com/medline/citation/32568687/COVID_19_Coronavirus_spike_protein_analysis_for_synthetic_vaccines_a_peptidomimetic_antagonist_and_therapeutic_drugs_and_analysis_of_a_proposed_achilles'_heel_conserved_region_to_minimize_probability_of_escape_mutations_and_drug_resistance_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0010-4825(20)30128-1 DB - PRIME DP - Unbound Medicine ER -