ABSTRACT
Aim. To propose a new type of antiviral treatment for COVID-19, pending the rollout of the developed vaccines and bypassing vaccine resistance of the new upcoming mutated virus variants. Aiming for prophylaxis and early therapy, the search focused on small molecules or repurposed, safe, oral and inexpensive drugs, also suitable for low-income countries. Methods. A search in peer-reviewed literature for preclinical antiviral mechanisms highlighted at last two clinical studies for further detailed clinical analysis: 1) High dose N-acetylcysteine (NAC) was successfully applied in very severe COVID-19-pneumonia;2) The discovery of serum level H2S (hydrogen sulfide) as a prognostic host factor. Results. Combining of these two findings resulted in a step-by-step approach with 3 perspectives that describes how H2S works in viral respiratory diseases, how H2S targets at least three vulnerabilities in the SARS-CoV-2 virus;finally, how H2S can be generated and with which drugs. More than 3 dozen successful, clinically well-documented applications have already been found. Conclusion. By using NAC as the H2S donor, the generated endogenous antiviral H2S reactivates the collapsed innate immunity, providing a therapy regimen for COVID-19. Further randomized controlled trials are warranted, considering antiviral H2S for inclusion in some master trial protocols. © 2021 Medical Education. All rights reserved.