Raman spectroscopy study of 7,8-dihydrofolate inhibition on the Wuhan strain SARS-CoV-2 binding to human ACE2 receptor.

Autor: Galván-Ojeda HJ; Coordinación para la Innovación y la Aplicación de la Ciencia y la Tecnología, Universidad Autónoma de San Luis Potosí, Av. Sierra Leona #550, Col. Lomas 2a, Sección, CP 78210 San Luis Potosí, SLP, Mexico., Acosta-Elias J; Facultad de Ciencias, Universidad Autónoma de San Luís Potosí, Álvaro Obregón 64, San Luis Potosí, SLP 78000, Mexico., Saavedra-Alanis VM; Facultad de Medicina, Universidad Autónoma de San Luís Potosí, Álvaro Obregón 64, San Luis Potosí, SLP 78000, Mexico., Espinosa-Tanguma R; Facultad de Medicina, Universidad Autónoma de San Luís Potosí, Álvaro Obregón 64, San Luis Potosí, SLP 78000, Mexico., Del Carmen Rodríguez-Aranda M; Coordinación para la Innovación y la Aplicación de la Ciencia y la Tecnología, Universidad Autónoma de San Luis Potosí, Av. Sierra Leona #550, Col. Lomas 2a, Sección, CP 78210 San Luis Potosí, SLP, Mexico., Hernández-Arteaga AC; Coordinación para la Innovación y la Aplicación de la Ciencia y la Tecnología, Universidad Autónoma de San Luis Potosí, Av. Sierra Leona #550, Col. Lomas 2a, Sección, CP 78210 San Luis Potosí, SLP, Mexico., Navarro-Contreras HR; Coordinación para la Innovación y la Aplicación de la Ciencia y la Tecnología, Universidad Autónoma de San Luis Potosí, Av. Sierra Leona #550, Col. Lomas 2a, Sección, CP 78210 San Luis Potosí, SLP, Mexico. Electronic address: hnavarro@uaslp.mx.
Jazyk: angličtina
Zdroj: Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy [Spectrochim Acta A Mol Biomol Spectrosc] 2024 May 05; Vol. 312, pp. 124050. Date of Electronic Publication: 2024 Feb 20.
DOI: 10.1016/j.saa.2024.124050
Abstrakt: Emerging evidence suggests that elevated levels of folic acid in the bloodstream may confer protection against Wuhan-SARS-CoV-2 infection and mitigate its associated symptoms. Notably, two comprehensive studies of COVID-19 patients in Israel and UK uncovered a remarkable trend, wherein individuals with heightened folic acid levels exhibited only mild symptoms and necessitated no ventilatory support. In parallel, research has underscored the potential connection between decreased folic acid levels and the severity of Covid-19 among hospitalized patients. Yet, the underlying mechanisms governing this intriguing inhibition remain elusive. In a quest to elucidate these mechanisms, we conducted a molecular dynamics simulation approach followed by a Raman spectroscopy study to delve into the intricate interplay between the folic acid metabolite, 7,8-dihydrofolate (DHF), and the angiotensin-converting enzyme ACE2 receptor, coupled with its interaction with the receptor-binding domain (RBD) of the Wuhan strain of SARS-CoV-2. Through a meticulous exploration, we scrutinized the transformation of the ACE2 + RBD complex, allowing these reactants to form bonds. This was juxtaposed with a similar investigation where ACE2 was initially permitted to react with DHF, followed by the exposure of the ACE2 + DHF complex to RBD. We find that DHF, when bonded to ACE2, functions as a physical barrier, effectively inhibiting the binding of the Wuhan strain RBD. This physicochemical process offers a cogent explanation for the observed inhibition of host cell infection in subjects receiving supplementary folic acid doses, as epidemiologically substantiated in multiple studies. This study not only sheds light on a potential avenue for mitigating SARS-CoV-2 infection but also underscores the crucial role of folic acid metabolites in host-virus interactions. This research paves the way for novel therapeutic strategies in the battle against COVID-19 and reinforces the significance of investigating the molecular mechanisms underlying the protective effects of folic acid in the context of viral infections.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors affirm that they do not have any known financial conflicts of interest or personal relationships that could have potentially influenced the findings presented in this study.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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