Table 3.
Mechanisms regarding antiviral activities of DMARDs and immunosuppressants.
| Medications | Viral susceptibility | Proposed antiviral mechanisms |
|---|---|---|
|
Chloroquine
HCQ |
SARS-CoV, HIV, dengue virus, chikungunya virus, influenza A virus, HCV, Zika virus | (1) Increase endosomal pH required for virus/cell fusion (2) Interfere with the glycosylation of cellular receptors |
| Cyclosporine A | HIV | Inhibit cyclophilins to incorporate into new virion, which is essential for virus infectivity |
| HCV genotype 1 | Inhibit host cyclophilins to form replication complex with NS5A/B of HCV, and influence protein folding and trafficking | |
| Flavivirus (Zika virus, dengue virus, West Nile virus, yellow fever virus) | Block the interaction between host cyclophilins and flaviviral NS5 protein | |
| Betaretrovirus | Interrupt life cycle from: (1) viral protein synthesis (2) gag and envelope assembly (3) particle budding |
|
| Hydroxyurea | HIV | (1) Inhibit DNA synthesis, slowing production of viral DNA (2) Deplete dNTP pools, which increase competitive ability of NRTIs to incorporate into HIV-1 DNA chain (3) Enhance NRTI phosphorylation, reducing resistance to NRTIs (4) Reduce cellular division of CD4+ T lymphocytes |
| HCV | Inhibit HCV RNA replication | |
| HBV | Unknown, inhibit HBV replication | |
| HSV | Inhibit HSV DNA replication | |
| Parvovirus B19 | Unknown | |
| Minocycline | HIV | (1) High affinity to HIV integrase and interaction with HIV integrase suppress the virus (2) Decrease viral expression from CD4+ T cells |
| Japanese encephalitis virus | Inhibit microglial activation and neuronal apoptosis | |
| Dengue virus | Reduce viral RNA synthesis, intracellular envelope protein expression, and the production of infectious virions | |
| RSV | (1) Reduce RSV-mediated cytopathic effects (2) Prevent RSV infection by affecting RSV F protein production or maturation |
|
| Enterovirus 71 | Reduce cytopathic effects and viral protein expressions | |
| Influenza virus | Reverse H7N9 replication | |
| West Nile virus | Anti-apoptotic properties result in neuroprotection. | |
| Reovirus | Reduce apoptosis and antigen expression | |
| Rabies | Reduce CD3+ cells may impair the host to control disease | |
| Mycophenolate mofetil/mycophenolic acid | HIV | Inhibit the dividing CD4+ T cells, and hence cytostatic and antiviral effect by depletion of this substrate |
| Influenza virus | Inhibit viral mRNA and protein expression via inhibition of cellular IMPDH | |
| MERS-CoV | Unknown | |
| Leflunomide | HSV, HIV, molluscum and verruca, CMV, BKV, RSV | Inhibit nucleocapsid tegumentation and thus prevents virion assembling |
| Tofacitinib | HTLV-1 | HTLV-1-induced ATLL is associated with JAK3 mutations; tofacitinib inhibits JAK3 |
| Thalidomide | HHV-8 | Unknown, suspect anti-angiogenesis and make immune system able to trigger antiviral response |
AAK1, AP2-associated protein kinase 1; ATLL, adult T-cell lymphoma/leukemia; BKV, BK virus; CMV, cytomegalovirus; DENV, dengue virus; DMARDs, disease-modifying anti-rheumatic drugs; DNA, deoxyribonucleic acid; dTNP, deoxynucleoside triphosphate; GAK, cyclin G-associated kinase; HAART, highly active antiretroviral therapy; HBV, hepatitis B virus; HCQ, hydroxychloroquine; HHV-8, human herpesvirus 8; HIV, human immunodeficiency virus; HTLV-I, human T-cell lymphotrophic virus-1; IMPDH, inosine monophosphate dehydrogenase; JAK, Janus kinase; MERS-CoV, Middle East respiratory syndrome coronavirus; mRNA, messenger RNA; NRTI, nucleoside analog reverse-transcriptase inhibitor; RCT, randomized-controlled trial; RNA, ribonucleic acid; RSV, respiratory syncytial virus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.