Majallah-i Dānishgāh-i ’Ulūm-i Pizishkī-i Īlām (Feb 2021)

Biological Evaluation of Coronaviruses and the Study of Molecular Docking, Linalool, and Thymol as orf1ab Protein Inhibitors and the Role of SARS-CoV-2 Virus in Bioterrorism

  • Bahman Fazeli nasab

Journal volume & issue
Vol. 28, no. 6
pp. 77 – 96


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Introduction: Coronaviruses are animal-derived enveloped viruses that in addition to respiratory and digestive diseases have also been found in neurological diseases, some of which have caused nephritis or have been observed in patients with Multiple Sclerosis and mouse hepatitis. However, in general, the most important effect of coronaviruses is on the respiratory and digestive systems. This study aimed to compare the genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-28) with that of other viruses of the coronavirus family. Moreover, it was attempted to investigate the possibility of its falsification and finally evaluate the effect of linalool and thymol on the inactivity of the orf1ab protein of SARS-CoV-2. Materials & Methods: The Coronaviridae family virus genome sequence was obtained from the NCBI database. After alignment, the number of mutations, nucleotide diversity, number of sites in which the same substitution occurred, clustering, similarity and genetic distance, as well as dN/dS index were evaluated in this study. The three-dimensional structure of the orf1ab protein prediction and the accuracy of the predicted model was also investigated. Furthermore, this study examined the motif and the domains conserved for the orf1ab gene in all viruses of the Coronaviridae family, as well as the membrane, cytoplasm, and kinase domains in the orf1ab virus of SARS-CoV-2. Regarding the molecular docking, linalool (the most important thirst-suppressing substance of Scrophularia striata) of the model plant (i.e., araboidopsis) and thymol (the most important ingredient of Trachyspermum ammi L.) were used to prevent the inactivation of the orf1ab protein of SARS-CoV-2.Ethics code: IR.UOZ.REC.1399.003 Findings: The SARS-CoV-2 virus has 11 conserved domains and 11 genes. The presence of the NSP13 superfamily and SUD-M superfamily in the SARS-CoV-2 virus genome indicate the ability and effort of this virus to be more stable in the environment. Based on the numerical value of dN/dS (1.036) and Tajima´s D (4.39) for orf1ab, the slope of the changes during evolution for the orf1ab gene is very slow, and there is no choice of direction in virus changes. Based on the highest interaction between linalool protein and orf1ab protein (-41.0), the highest accuracy (0.172), lowest energy level (ΔG=-6.23Kcal/mol), and the best combination (Full Fitness=-1340.18 Kcal/mol) between thymol phytochemical and orf1ab protein, molecular docking results showed that both linalool protein and thymol substance bound to orf1ab protein and inhibited its activity. Discussions & Conclusions: Linalol and thymol affected the inactivity of the orf1ab protein in the SARS-CoV-2 virus. However, clinical trials on linalool and thymol should be performed to confirm these hypotheses. If the hypothesis approves, it is suggested to use them in this regard. In addition, by examining the dN/dS indices, as well as evaluating the singletons, domains, and conserved areas of all viruses, it was found that the SARS-CoV-2 virus could not be purposefully manipulated.