Table 3.
Antiviral drugs proposed against SARS-CoV-2 infection displaying antitumor effects.
| Antiviral drugs | FDA indication | Anti-CoV-2effectin vitro | Antitumor effectin vitro | Antitumor effectin vivo | Anticancer mechanism | Ongoing clinical trialsfor viral or cancerindications |
| Azithromycin | Acute bacterial sinusitisAcute bacterialinfections in COPDCommunity-acquired pneumoniaPharyngitis/tonsillitis Skin infectionsUrethritis and cervicitis Genital ulcer disease | Yes (Andreani et al., 2020) | BC cellsPancreatic cancerCells (Mukai et al., 2016) HCC cells (Abdel-Hamid et al., 2017) Colon cancer, GCCells (Qiao et al., 2018) Myeloma cells (Moriya et al., 2013) | In miceLung cancer (Moriya et al., 2013) | Inhibition of angiogenesis (suppression of VEGF receptor 2 signaling) Apoptosis via both intrinsic and extrinsic pathway (Abdel-Hamid et al., 2017) | NCT04341207: (+hydroxychloroquine) SARS-CoV-2 incancer patients;NCT04369365:COVID-19 prophylaxisin cancer patients;NCT04392128:(+hydroxychloroquine) COVID-19 treatmentin patients withhematologicalmalignancies |
| Camostat mesylate | No | Yes (Hoffmann et al., 2020) | No | No | No | No |
| Favipiravir | No | Yes (Wang et al., 2020b) | No | No | No | No |
| Hydroxychloroquine | COVID-19 (Chinawith cautions)MalariaAutoimmuneDiseases | Yes (Liu et al., 2020b) | Glioblastoma cells (Kim et al., 2010) Stomach cancer Cells (Kim et al., 2019) Pancreatic cancerCells (Yang et al., 2014) Kidney cancercells (Park et al., 2016) Endometrial cancer cells (Fukuda, T. et al. 2015) MyelomaCells (Jarauta et al., 2016) LymphoblasticCells (Hounjet et al., 2019) Lymphoma cells (Masud et al., 2016)Melanoma cells (Lakhter et al., 2013) | In mice:Neuroblastoma(Cournoyer et al., 2019) Gastric cancer (Wang et al., 2019) Prostate cancer (Saleem et al., 2012)Melanoma (Hall et al., 2018)In humans:Phase 1 trialin melanoma,glioblastoma andmyeloma (Saleem et al., 2012) | Autophagy inhibition (Levy et al., 2017) Akt signaling pathway inhibition G2/M cell cycle arrest (Jiang et al., 2008) Increase in CTLResponse (Xu et al., 2014) | Viral indications:NCT04341207: SARS-CoV-2 in cancer patients; NCT04381988:COVID-19 prevention in patients receivingRT; NCT04392128:(+ azithromycin)COVID-19 andhematologicalmalignancyCancer indications:NCT01266057,NCT01023737,NCT01480154: advancedcancer; NCT03774472,NCT03774472,NCT03032406:BC; NCT03377179:cholangiocarcinoma;NCT04214418,NCT04145297:gastrointestinaladenocarcinoma;NCT04201457:glioma; NCT03037437:HCC; NCT02722369,NCT00977470: lungcancer; NCT04163107:myeloma; NCT03754179,NCT02257424:melanoma;NCT03081702: ovariancancer; NCT03598595:osteosarcoma;NCT04132505,NCT03825289,NCT01506973,NCT01494155:pancreatic cancer;NCT03513211,NCT04011410,NCT04011410: prostatecancer; NCT01023737,NCT03015324,NCT04316169: solidtumors |
| Lopinavir | HIV | Yes, at very high dose (Choy et al., 2020) | Primary effusionlymphoma cells (Kariya et al., 2014)Melanoma cells (Paskas et al., 2019)Lymphoblastic and myeloid leukemia Cells (Maksimovic et al., 2015) | In mice:Prostate cancerColon cancer (Selvakumaran et al., 2013) | Caspase-dependentApoptosis (Kariya et al., 2014) Suppression of NF-κB activity by inhibition of KK phosphorylation in PEL cells (Kariya et al., 2014) Inhibition of proliferation,Transient activation of Akt and inhibition of P70 S6 kinase (Paskas et al., 2019) ER stressCell signaling induction, including Akt and mTOR (Meier et al., 2017) | No |
| Nitazoxanide | Giardia lambliadiarrhea; Cryptosporidiumparvum diarrhea | Yes (Anastasiou et al., 2020) | Glioblastoma cells (Wang et al., 2018) | In mice:CRC (Senkowski et al., 2015) | G1-phase cell cyclearrest, inhibition ofprotein translation viathe mTOR–c-Myc–p27 pathway (Ripani et al., 2020) | No |
| Nafamostat | No | Yes (De Felice et al., 2020) | GC cells CRC cellsGallbladder cancer cellsPancreaticcancer cellsHCC cells (Haruki et al., 2013) | In mice:HCC (Haruki et al., 2013) GallbladderCancer (Iwase et al., 2013)PancreaticCancer (Gocho et al., 2013) | Induce mitochondria dependent apoptosisCanonical NF-κBsignaling blockadeTNFR1-stimulatedcleavage of caspasefamily members (Iwase et al., 2013) | No |
| Oseltamivir | Influenza virusinfection | Limited(Srinivas et al., 2020) | BC cells (Thulasiraman et al., 2019) | In canines and mice: Increasemammary tumoraggressiveness(deOliveira et al., 2015) | Increase of cleavedcaspase 3 expression (Thulasiraman et al., 2019) | No |
| Penciclovir | Recurrent herpes labialis | Yes (Hongyan et al., 2020) | Oral hairyLeukoplakia (Moura and Haddad, 2010) | No | Accumulation ofcells in S phase andapoptotic death (Shaw et al., 2001) | No |
| Ribavirin | HCVHCC co-infectedwith HIV | Yes (Wang et al., 2020c) (high dose) | Glioblastoma cells (Volpin et al., 2017)HNSCC cells (Dunn et al., 2018) Cervical and colon cancer cells (Xi et al., 2018) | In mice:Glioma, Glioblastoma (Volpin et al., 2017)RCC291 | GTP depletion in HeLa cervical cancer cells (Volpin et al., 2017) Growth inhibition, STAT1 depletion and IFNγ (Dominguez et al., 2019) | NCT02109744:AML; NCT01268579,NCT02308241:HPV-related malignancies;NCT03585725: indolent follicular lymphoma and mantle cell lymphoma;NCT02940496: livercancer; NCT01268579:tonsil and/or base oftongue SCC |
| Ritonavir | HIV | No | ThymomasEL4-T cells (Moawad 2014)Cervical cancerCells (Bandiera et al., 2016) Myeloma cells (Dalva et al., 2015) Lymphoblastoid B cells (Dewan et al., 2009) | In mice:Thymoma (Moawad 2014)Prostate cancer (Ikezoe et al., 2004) In humans:Glioma—noEfficacy (Laurent et al., 2004) | Cell signaling induction including Akt and mTOR (Dalva et al., 2015) Suppression ofpro-survival BCL-2family member andMCL-1 expression (Dalva et al., 2015) Suppression ofNF-κB transcriptionalActivation (Dewan et al., 2009) | NCT02948283: multiplemyeloma, CLL |
| Umifenovir | No | Yes (Wang et al., 2020) | No | No | No | No |
BC, breast cancer; BCL-2, B cell lymphoma 2; CLL, chronic lymphocytic leukemia; COPD, chronic obstructive pulmonary disease; CTL, cytotoxic T lymphocytes; CRC, colorectal cancer; eIF4E, eukaryotic initiation factor 4; ERK, extracellular signal-regulated kinase; EZH2, enhancer of zeste homolog 2; GC, gastric cancer; HCC, hepatocellular carcinoma; HNSCC, head and neck squamous-cell carcinoma; HPV, human papillomavirus; IL, interleukin; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor-κB; NSCLC, non-small-cell lung cancer; RCC, renal-cell carcinoma; SCC, squamous-cell carcinoma; STAT1, signal transducers and activators of transcription protein; TNF-α, tumor necrosis factor-α; VEGF, vascular endothelial growth factor.