Table 2.
Drugs with anti-cancer effects and redeployment to become anti-virals.
| Drugs | Mode of action | Cancer indication | Antiviral indication | Type of study | Ongoing clinical trials |
| Interferon-based therapies | |||||
| IFNα2b or IFNβ1b, alone or combined with antivirals | Stimulation of innateimmunity | RCC, melanoma,HCC, CML, hairy-cell Leukemia (Galimberti et al., 2020),AIDS-relatedKaposi sarcomaFollicular lymphomaCondylomata acuminata | Hepatitis B and C | Clinical trial againstCOVID19 (Sallard et al., 2020; Lu, H., 2020; Sheahan et al., 2020) | NCT04344600, NCT04350671, NCT04343768, NCT04343976, NCT04254874, NCT04320238, ChiCTR2000029387, NCT04315948, NCT04276688 |
| IFNγ | Activation of lungmacrophages | Cancer (Garcia et al., 2018) cancercomorbidities: e.g., COPD, idiopathicpulmonary fibrosis | Synergy with IFNβ to block SARS-CoV-2 replication | Clinical trial withinhaled IFNγ (Smaldone, 2018) | |
| TLR3 agonistsHiltonol(poly-ICLC) | Induction of type IIFNs and protectionagainst respiratoryvirus–inducedimmunopathology (Kumaki et al., 2017) | Adjuvant for cancer vaccines Therapeutic in addition to immunogenic chemotherapy | Preclinical studyin BALB/c miceagainst SARS-CoV: prophylactic and therapeutic effects of poly-ICLC by intranasal route (Kumaki et al., 2017) | No trials | |
| Immune checkpoint inhibitors | |||||
| Anti-PD-1 AbsPembrolizumabNivolumab | Reactivation of exhausted antiviral and antitumor CTLs (Hirsch et al., 2017) | Multiple stage IIIc IV cancer indications (various cancers) (Hirsch et al., 2017) | Prevention of EBV-induced HLH (Liu et al., 2020a) Non-inferiority in case of concomitant NSCLC and COVID-19 (Luo et al., 2020b) | Retrospective analysis on (Weiss et al., 2013) patients with lung cancer adjusted for gender and smoking status Randomized trials with anti-PD-1 | NCT04335305: pembrolizumabNCT04333914: nivolumab |
| IL-6–JAK–STAT3 | |||||
| Anti-IL-6R AbsTocilizumab | Cytokine storm andHLH, prevention ofimmunothrombosis,lung and systemicinflammation,reduction ofneutrophilia (Moots et al., 2017) | FDA approved foriatrogenic responsesto immunostimulation (e.g., CART cell therapies) andmyeloproliferativeneoplasms.In assessment formultiple myeloma,many solid andhematologicalmalignancies andacute GVHD (Ocana et al., 2017) | FDA approved in China for severe COVID-19 | Pilot studies orRandomized clinical trials Observationalstudy in 21 Chinesepatients withCOVID-19TranslationalResearch studies (Guo et al., 2020; Liao et al., 2020) | NCT04332094, NCT04359667, NCT04317092, NCT0433291, NCT04335071, NCT04346355, NCT04306705, NCT04331795, NCT04377659, NCT04377750, NCT04363853, NCT04320615, NCT04315480, NCT04331808, NCT04310228, NCT0433391, NCT04339712, NCT04331808 |
| Androgen-deprivation therapy | |||||
| Androgenreceptordeprivationtherapies (ADT) | ADTs decreaseTMPRSS2 in lungand prostatetissues (Mikkonen et al., 2010) | Prostate cancer(expressing TMPRSS2) (Lucas et al., 2014) | TMPRSS2 inducesspike protein priming;its inhibition bycamostat mesylatehas antiviral effect | Retrospective Italian study, n = 4532 patients; ADT decreased COVID-19 incidence(OR: 4.05) (Lucas et al., 2014) | NCT04397718 |
| Other small molecules | |||||
| Anti-CD26/DDP4Begelomab | Alternate receptorfor SARS-CoV-2 (inaddition to ACE2) (Vankadari and Wilce 2020) Preservation of Cxcl10 biologicalactivity and anticancer synergisticeffects betweenCD26 blockade andanti-PD-1 Ab (Nabavi et al., 2020) | Steroid refractory acute GVHD(Nabavi et al., 2020) | MERS Diabetes (Iacobellis, 2020) | No trials | |
| ImatinibMesylate or saracatinib | Abl kinase activityinvolved incoronavirus fusionwith endosomalmembrane as well ascell–cell fusion latein infection (Inoue et al., 2007) | FDA approved for CML and GIST | Infectious bronchitisvirus (IBV)SARS-CoV1MERS (Nabavi et al., 2020) | Randomized clinical trial | NCT04357613, NCT04356495,NCT04346147 |
| Ibrutinib | TKI Bruton kinaseand IL-2-inducibleT cell kinaseinhibitor that bluntsT cell activation andreduces cytokinerelease syndrome (Treon et al., 2020) | Steroid-refractorychronic GVHDCLL Waldenström disease (Galimberti et al., 2020) | Effects on host immunecells; no direct antiviralactivity | Retrospective observation in Waldenstrommacroglobulinemia: reduced COVID-19incidence (Treon et al., 2020) | No trials |
| Zotatifin;Plitidepsin | eIF4A inhibitor;eEF1A inhibitor | Preclinical activity against multiple forms of KRAS mutant andreceptor tyrosine kinase mutant cancers currentlybeing evaluated inmultiple myeloma | eIF4H, an Nsp9interactor, is a partner ofeIF4A; eIF4A inhibitorzotatifin shows strongantiviral effect eIF4Ainhibitor ternatin-4 hasantiviral effects | Phase 1/2 clinicaltrial in patients witha targeted set ofsolid tumors (Gordon et al., 2020) | NCT04092673NCT04382066 |
| Anakinra | Interleukin (IL)−1receptor antagonist | Currently beingevaluated to prevent or treat severe side effectsin patients receiving CAR-T cell therapy (NCT04148430) | Clinical trials incytokine stormsyndrome secondaryto COVID-19 (Cavalli et al., 2020) | NCT04443881 | |
| Other strategies | |||||
| BCG | Trained immunityEpigeneticreprogrammingof myeloid cells (Mitroulis et al., 2018) | FDA approved innon-muscle invasivebladder urothelialcancers | No dataNegative epidemiologicaldata (Hamiel et al., 2014) | Phase 3 randomized controlled clinicaltrials | NCT04328441, NCT04327206,NCT04379336, NCT04327206,NCT04348370 |
| Chlorpromazine | High concentrationsin lung and salivaAnti-inflammatory(more IL10, less TNFα, IFNα)Antiproliferativevia suppressionof AKT–mTOR orsirtuin 1 inhibition | Phenothiazinederivative used to treat psychotic disordersControl of nauseaand vomiting incisplatin-treated cancer patientsWeak indication in drug repurposing:antineoplastic properties in colon cancer and glioblastoma in vitro | Inhibition of clathrin-dependent endocytosis(Gadina et al., 1991) | Clinical trials | NCT04366739, NCT04354805 |
| Low-doseRadiotherapy | ImmunomodulationReprogrammingof iNOS+/ M1 phenotype of pulmonary macrophages(Meziani et al., 2021) | Low-grade lymphomaLung cancer | Pneumonia | Preclinical models oflung inflammationinduced by TLR3 orTLR4L (Meziani et al., 2021) | NCT04377477, NCT04390412,NCT04366791, NCT04380818,NCT04394182 |
| Vitamin D3(cholecalciferol) | Extra skeletalbioactivity inprevention ofinfections, T1D andT2D, cardiovasculardisease, obesity,asthma, inflammatorybowel disease andcancers (colon,breast, prostate andovarian) | Induction of apoptosis,stimulation of celldifferentiation andanti-inflammatoryand antiproliferativeeffects and inhibition ofangiogenesis, invasionand metastasisReduction of death bycancer but no benefitin preventing cancer incidence. | Protective effect ofvitamin D in settings ofpneumonia, cytokinehyperproduction andARDS (Huang et al., 2020)Vitamin D repurposedfor influenza A H5N1virus–induced lunginjury | Observationalstudies: Dailysupplementation with 2000–5000 IU/day vitamin D3 in older adults with Parkinson disease may offer protection against COVID-19 (Hribar et al., 2020; Manson et al., 2019)Genetic studies:Vitamin D receptorgene (VDR)alleles associatedwith increased susceptibility to respiratory or viral infections (Jolliffe et al., 2018) | NCT04399746,NCT04344041,NCT04372017, NCT04386850 |
Ab, antibody; ADT, androgen deprivation therapy; ARDS, acute respiratory distress syndrome; CML, chronic myeloid leukemia; CLL, chronic lymphocytic leukemia; EBV, Epstein–Barr virus; EMA, European Medical Agency; GVHD, graft-versus-host disease; HCC, hepatocarcinoma; HLH, hemophagocytic lymphohistiocytosis; iNOS, inducible nitric acid synthase; NSCLC, non-small-cell lung cancer; poly-ICLC, polyinosinic–polycytidylic acid; RCC, renal-cell carcinoma.