The endogenous free radical nitric oxide (NO) plays a pivotal role in the immunological system. NO has already been reported as a potential candidate for use in the treatment of human coronavirus infections, including COVID-19. In fact, inhaled NO has been used in clinical settings for its antiviral respiratory action, and in the regulation of blood pressure to avoid clot formation. In this mini-review, we discuss recent progress concerning the antivirus activity of NO in clinical, pre-clinical and research settings, and its beneficial effects in the treat-ment of clinical complications in patients infected with coronaviruses and other respiratory viral diseases, including COVID-19. We also highlight promising therapeutic effects of NO donors allied to nanomaterials to combat COVID-19 and other human coronavirus infections. Nanomaterials can be designed to deliver sustained, localized NO release directly at the desired application site, enhancing the beneficial effects of NO and mini-mizing the side effects. Challenges and perspectives are presented to open new fields of research.