Nitric oxide is an endogenous signaling molecule that is involved in a host of biological processes. The molecule is produced internally by the action of nitric oxide synthase enzyme that catalyzes its production from L-arginine. The antimicrobial activity of nitric oxide has been described against several protozoal and bacterial pathogens as well as against some viruses (herpes simplex virus 1, neurotropic murine coronavirus, and murine hepatitis virus strain 3) [267,268,269]. The role of nitric oxide in SARS-CoV infection was earlier investigated in Vero E6 cells by using the nitric oxide donor S-nitroso-N-acetyl-penicillamine. The study revealed that the nitric oxide donor substantially inhibited the replication of SARS-CoV in a concentration-dependent fashion (0–400 µM). Nitric oxide inhibited the viral protein and RNA synthesis. Importantly, the study demonstrated that nitric oxide produced by inducible nitric oxide synthase inhibited the replication of SARS-CoV [270]. Another study revealed that nitric oxide causes a reduction in the palmitoylation of the viral spike S protein. This subsequently impedes the fusion between the viral spike S protein and the host ACE2. Moreover, nitric oxide also leads to a substantial decrease in viral RNA production in the early steps of viral replication [271]. These outcomes were attributed to its potential effect on the cysteine proteases of SARS-CoV [272]. Given that the genome of SARS-CoV is significantly similar to SARS-CoV-2, the inhaled nitric oxide therapy in COVID-19 patients is predicted to produce the same effects [273].