ABSTRACT
The causative agent of coronavirus disease-2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enters the host cells via an angiotensin-converting enzyme 2 (ACE2)-mediated endocytosis-dependent manner. Because ACE2 is highly expressed in the heart, SARS-CoV-2 can severely infect heart tissue and arteries, causing acute and chronic damage to the cardiovascular system. Therefore, special attention should be paid to finding appropriate agents to protect this vital system during COVID-19 treatment. Papaverine is a unique vasodilator alkaloid that is clinically used in the treatment of vasospasm. Interestingly, this compound has potent and direct effects on a wide range of viruses, and could also prevent viral exploitation mechanisms of the host cell facilities by inhibiting some cellular signaling pathways such as p38 MAPK. This pathway was recently introduced as a promising target for the treatment of COVID-19. Papaverine also has anti-inflammatory effects which is useful in combating the hyper-inflammatory phase of the COVID-19. Unlike some medications that have severe dosage-restrictions in the treatment of COVID-19 due to cardiac side effects, papaverine is recommended for use in many heart disorders. The ability of papaverine to treat COVID-19 has become more promising when the results of some extensive screenings showed the strong ability of this compound to inhibit the cytopathic effects of SARS-CoV-2 with EC50 of 1.1 µM. Having several therapeutic effects along with desired safety profile raises this hypothesis that papaverine could be a promising compound for the suppression of SARS-CoV-2 and prevention of ischemia/vasoconstriction-related complications in COVID-19 disease, especially in patients with underlying cardiovascular diseases (CVDs).