f) Protease inhibitors
Cinanserin , a known serotonin antagonist, which also showed hopeful SARS-CoV inhibitory features, is another possible option to be considered. It could inhibit the 3 chymotrypsin‐like protease and could inhibit SARS‐CoV replication (45). The 3C-L protease is encoded in SARS‐CoV2. Therefore, Cinanserin may be an effective therapy for the COVID‐19 infection. Also, flavonoids like: Herbacetin, rhoifolin, and pectolinarin are 3C‐like protease inhibitors (8).
Nelfinavir is an HIV-1 protease inhibitor previously used in HIV treatment that acts through inhibition of 3C-L protein (45).
Carfilzomib is an approved anti-cancer drug which by inhibition of proteasome shows potential for inhibiting COVID-19 protease (46).
Indinavir: It is an anti-HIV drug that based on molecular studies can also be used against SARS-COV-2 by potentially inhibiting the viral protease. Adverse effects are mostly of gastrointestinal and hepatic symptoms (47, 48).
Danoprevir: It is another HCV NS3/4 protease inhibitor has also shown potential according to the studies. It is also being used for Hepatitis C treatment. Studies reveal a pharmacokinetic boost in co-administration of danoprevir with ritonavir (49).
Ledipasvir and velpatasvir , NS5A protein inhibitors of HCV have been proposed for further investigation due to virtual screening studies. Ledipasvir and velpatasvir in combination withsofosbuvir have been used as a potent anti-hepatitis C treatment. They may also cause headache, fatigue, and nausea as adverse effects (50).
SARS-CoV-2 M protein is the main enzyme utilized by the virus for replication, thus making it an appealing target. Studies suggest multiple agents that may or may not be approved by the FDA. For example:Telaprevir and boceprevi r. These are α-ketoamide drugs that target the main protease of coronaviruses and 3C protease of enteroviruses and have a crucial role in the treatment of hepatitis C (51).