SARS-CoV-2 Infection, Sex-Related Differences, and a Possible Personalized Treatment Approach with Valproic Acid: A Review

• Published in: Biomedicines Vol. 10; no. 5; p. 962
• Main Authors: Stakišaitis, Donatas, Kapočius, Linas, Valančiūtė, Angelija, Balnytė, Ingrida, Tamošuitis, Tomas, Vaitkevičius, Arūnas, Sužiedėlis, Kęstutis, Urbonienė, Daiva, Tatarūnas, Vacis, Kilimaitė, Evelina, Gečys, Dovydas, Lesauskaitė, Vaiva
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21-04-2022; MDPI
• Subjects: clinical research; Clinical trials; Coronaviruses; COVID-19; Cytokines; Disease; Enzymes; Females; Gender differences; Gene expression; Histone deacetylase; Immunomodulation; Immunosuppressive agents; Infections; Inflammation; Lungs; Males; Medical research; Metabolism; Metabolites; Plasma; pre-clinical research; Proteins; Review; RNA polymerase; Severe acute respiratory syndrome coronavirus 2; Sex differences; Testosterone; Valproic acid; Viral infections; Womens health; X chromosomes; COVID-19; pre-clinical research; valproic acid; clinical research; sex differences
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines10050962

Sex differences identified in the COVID-19 pandemic are necessary to study. It is essential to investigate the efficacy of the drugs in clinical trials for the treatment of COVID-19, and to analyse the sex-related beneficial and adverse effects. The histone deacetylase inhibitor valproic acid (VPA) is a potential drug that could be adapted to prevent the progression and complications of SARS-CoV-2 infection. VPA has a history of research in the treatment of various viral infections. This article reviews the preclinical data, showing that the pharmacological impact of VPA may apply to COVID-19 pathogenetic mechanisms. VPA inhibits SARS-CoV-2 virus entry, suppresses the pro-inflammatory immune cell and cytokine response to infection, and reduces inflammatory tissue and organ damage by mechanisms that may appear to be sex-related. The antithrombotic, antiplatelet, anti-inflammatory, immunomodulatory, glucose- and testosterone-lowering in blood serum effects of VPA suggest that the drug could be promising for therapy of COVID-19. Sex-related differences in the efficacy of VPA treatment may be significant in developing a personalised treatment strategy for COVID-19.