Biological plausibility and therapeutic options.
| Viral Mechanism | Drug Rationale | Suggested Therapy | Current Research Status |
|---|---|---|---|
| The SARS-CoV-2 after entering the cell, uses the cellular machinery to synthesize and secrete a mature virion2. | Inhibition of RNAP and protease | Inhibitors of RNAP (e.g., remdesivir and favipiravir) and protease inhibitors (e.g., lopinavir and ritonavir) | Primary studies with lopinavir/ritonavir did not show clinical improvement or reduction in mortality2. The use of remdesivir in rhesus macaques infected with SARS-CoV-2 was effective in reducing clinical disease and lung damage7. |
| The TMPRSS2 protease cleaves coronavirus fusion glycoproteins (called spike proteins), which induces virus–cell membrane fusion at the cell surface and facilitates entry of coronaviruses into the host cell3. | Inhibition of TMPRSS2 | Camostat mesylate | There are no clinical trials specifically testing these drugs as yet, although there are studies suggesting its off-label use3. |
| The mature virion interacts with TLR to stimulate inflammatory pathways and regulate the production of proinflammatory cytokines4. | Inhibition of endosomal TLR activation | Chloroquine and HCQ | Some studies showed no effectiveness4 while others showed reduction in the recovery time for cough and fever8. |
| JAK 1 and 2 are implicated in inflammation pathways, and the enzyme AAK1 works in viral cellular entry2. | Inhibition of JAK 1/2 (and consequently) AAK1 | Baricitinib | A small, open-label, non-randomized pilot study with patients presenting moderate COVID-19 pneumonia showed that in the baricitinib-treated group, all clinical characteristics and respiratory function variables significantly improved when compared to baseline9. |
| IL-6 production through TLR. IL-6 induces lung inflammation, fever, and fibrosis10. | IL-6 inhibition | TCZ, sarilumab | A small retrospective study observed that symptoms, hypoxemia, and CT opacity changes were improved shortly after the treatment with tocilizumab (IL-6 blocker), suggesting that inhibition of IL-6 pathway could be an efficient target for the treatment of COVID-1910. |
RNAP: RNA polymerase; TLR: Toll-like receptors; HCQ: hydroxychloroquine; JAK: Janus kinase; AAK1: AP-2–associated protein kinase 1; COVID-19: coronavirus disease 2019; IL: interleukin; TCZ: tocilizumab; CT: computed tomography.