TABLE 1.
Study of the antiviral effect of FDA-approved drugs, STAs, EZE, and MET.
| Lipid-lowering drug | Virus | Study type | Effect | References |
| LOV and FLV | DENV | In vitro: Human Peripheral blood mononuclear cells (PBMC) and A459 cells. | Inhibition of viral replication. | Rothwell et al., 2009 |
| LOV | DENV | In vitro: Human endothelial cell line HMEC and Vero cells | Inhibition of viral assembly. | Martínez-Gutierrez et al., 2011 |
| LOV and PRV | DENV | In vitro: Huh-7 cells | Reduction of virus yield and viral RNA transcripts. | Soto-Acosta et al., 2013 |
| LOV | DENV | In vivo: AG129 Mice | Delayed infection and increased survival rate. | Martinez-Gutierrez et al., 2014 |
| FLV, ATV, LOV, PRV and SIM | DENV | In vitro: Huh-7 cells | Reduction of viral yield by modulation of the cellular antiviral profile. | Bryan-Marrugo et al., 2016 |
| LOV | DENV | Randomized, Double-Blind, Placebo-Controlled Trial: 300 Vietnamese adults with a positive dengue NS1. | No evidence of a beneficial effect of statins on any of the clinical manifestations or on dengue viremia. | Whitehorn et al., 2016 |
| LOV | DENV | In vitro: Huh-7 cells | Disruption in the formation of replicative complexes. | Soto-Acosta et al., 2017 |
| SIM, LOV, RSV, and PRV | DENV | Retrospective cohort study: 257 adult dengue patients with hyperlipidemia. | Statin use was not associated with a lower risk of FHD/DSS. | Chia et al., 2018 |
| ATV, CRV, FLV, LOV, MEV, and SIM | ZIKV | In vitro: Vero cells | Reduction of virus yield. | Españo et al., 2019 |
| LOV | ZIKV | In vitro: Huh-7 cells | Reduction of infected cells. | Farfan-Morales et al., 2021 |
| ATV | JEV |
In vitro: Neurosphere culture from SVZ region from BALB/c mouse pup brains In vivo: BALB/c mouse |
In vitro: reduction of cell death. In vivo: Reduction of viral load in the SVZ. Inhibition of microglial activation and proinflammatory cyto/chemokine production. |
Wani et al., 2020 |
| LOV | RSV |
In vitro: HEp-2 cells In vivo: C57BL/6 or BALB/c mice |
In vitro: Reduction of viral replication. In vivo: Reduction of viral replication and virus-induced illness score in mice. |
Gower and Graham, 2001 |
| LOV | RSV | In vitro: murine RAW 264.7 (RAW) macrophage cell line and primary murine lung macrophages. | Treatment mitigates the pro-inflammatory cytokine response. Lovastatin treatment did not inhibit RSV infection. |
Ravi et al., 2013 |
| FLV | HCV | Clinical Trials: Patients with chronic HCV | Lower HCV RNA titers | Bader et al., 2008; Forde et al., 2009 |
| MEV and PTV. | HCV | In vitro: Replicon system in hepatocyte cells. | Reduction of replication | Delang et al., 2009; Moriguchi et al., 2010 |
| PTV | HCV | Retrospective and prospective randomized pilot study: HCV Patients with genotype 1b. | Reduction of viral load and enhancement of the SVR | Shimada et al., 2012; Yokoyama et al., 2014 |
| SIM | HBV | In vitro: HepG2.2.15 | Inhibition of replication. | Bader and Korba, 2010 |
| ATV | HBV | Case Report | Hepatitis B virus reactivation associated with ATOR | Wu, 2013 |
| FLV | CMV | In vitro: HUVECs | Decreased viral DNA concentration, viral particle concentration and replication. | Potena et al., 2004. |
| LOV, FLV, SIM, ATV, RSV, and PTV | EBOV | In vitro: Primary human monocyte-derived macrophages and Huh-7 cell line. | Decreased infection. Reduction of the infectivity of the released viral particles. | Shrivastava-Ranjan et al., 2018 |
| SIM | EBOV | In vitro: transfected HeLa cells with FLAG-GPs. | Reduction of EBOV glycoprotein-mediated cytotoxicity. | Hacke et al., 2015. |
| FLV | IAV (H1N1) | In vitro: MDCK and A549 cells | Reduction of viral RNA and proteins. Protects host cells against influenza-induced inflammation. |
Peng et al., 2014 |
| LOV/caffeine combination | IAV (H5N1,H3N2 and H1N1) | In vivo: BALB/c mice | LOV/caffeine combination effectively ameliorated lung damage and inhibited viral replication | Liu et al., 2009 |
| ATV, CRV, FLV, LOV, PRV, and SIM | IAV (H1N1) | Cohort study over 10 influenza seasons (1996 to 2006) using linked administrative databases in Ontario, Canada. | Reduced risk of mortality | Kwong et al., 2009 |
| STAs (not specified) | IAV and IBV (H1N1) | Retrospective analysis: 526 hospitalized patients from Israel with laboratory-confirmed 2017-2018 influenza. | Use of STAs was not associated with mortality benefit. | Atamna et al., 2019 |
| LOV | HIV-1 |
In vivo: SCID mice grafted with adult human PBMCs Clinical trial: Patients in A1 disease stage |
Reduction in viral load and increase in CD4+ T-cell count | del Real et al., 2004 |
| ATV, RSV, SIM, PRV, FLV and PTV | SARS-CoV-2 | Retrospective study: 13,981 patients with COVID-19 in Hubei Province, China; 2921 patients COVID-19, who are hospitalized in 150 Spanish hospitals. | Reduced risk of mortality among people with COVID-19 | Zhang et al., 2020; Torres-Peña et al., 2021 |
| EZE | HCV |
In vitro: Huh-7 cells In vivo: Chimeric mice, uPA/SCID mice with human hepatocytes. |
Inhibition of Infection In vitro and In vivo EZE potently blocks HCV uptake and delays the establishment of HCV genotype 1b infection in mice with human liver grafts. | Sainz et al., 2012 |
| EZE | HBV | In vitro: Differentiated HepaRG cells. | EZE inhibits the establishment of intrahepatic cccDNA and expression of viral replication markers. | Lucifora et al., 2013 |
| EZE | DENV | In vitro: Huh-7 cells. | Decreased infected cells, viral yield, viral RNA and protein synthesis. Cholesterol-dependent antiviral effect. |
Osuna-Ramos et al., 2018a |
| MET | DENV | In vitro: Huh-7 cells. | Disruption in the formation of replicative complexes. Inhibition of viral yield, protein, and cell infection. | Soto-Acosta et al., 2017 |
| MET | DENV | Retrospective cohort study: 223 DENV patients with diabetes mellitus. | Lower risk of suffering a severe disease caused by DENV. | Htun et al., 2018 |
| MET | DENV |
In vitro: Huh-7 cells In vivo: AG129 mice |
In vitro: Decreased viral yield, protein, and percentage of infected cells. In vivo: Reduced virus-induced illness score in mice and increased survival rate. |
Farfan-Morales et al., 2021 |
| MET | ZIKV |
In vitro: Huh-7 cells In vivo: AG129 mice |
In vitro: Decreased viral yield, protein, and percentage of infected cells. In vivo: No evidence of a beneficial effect. |
Farfan-Morales et al., 2021 |
| MET | YFV | In vitro: Huh-7 cells | In vitro: Decreased viral yield, protein, and percentage of infected cells. | Farfan-Morales et al., 2021 |
| MET | HCV | Randomized Controlled Trial: 98 patients with genotype 1 chronic hepatitis C and insulin resistance | The combination of MET, peginterferon alfa-2a, and ribavirin increased the SVR rate of patients with hepatitis C genotype 1, with a good safety profile. | Yu et al., 2012 |
| MET | HCV | In vitro: OR6 cells and Huh 7.5.1 cells. | Activation of type I interferon signaling. Reduction of replication via AMPK. |
Tsai et al., 2017 |
| MET + SIM combination | HCV | In vitro: Huh7.5 cells. | Treatment with both drugs inhibited Huh7.5 cell growth and HCV infection via mTOR. | Del Campo et al., 2018 |
| MET | HBV | In vitro: HepG2 and HepG2.2.15 cell line | Moderate inhibition of HBV replication. | Xun et al., 2014 |
| MET | CVB3 | In vitro: Hela cells and primary myocardial cells | Inhibition of replication by reducing lipid accumulation through suppression of lipid synthesis-associated gene expression. | Xie et al., 2015 |
| MET | KSHV |
In vitro: primary human umbilical vein endothelial cells In vivo: BALB/c mice |
In vitro: Inhibition of viral replication, viral lytic gene expression and production of infectious virions. In vivo: Decreased viral replication and increased survival rates. |
Cheng et al., 2016 |
| MET | SARS-COV2 | Retrospective studies: 283 Hospitalized diabetic patients with confirmed COVID-19 in the Tongji Hospital of Wuhan, China. 1139 COVID-19 positive patients in 8 states in United States. 775 nursing Home Residents Infected with SARS-CoV2 from the Community Living Centers (CLC), United States. |
Antidiabetic treatment with metformin was associated with lower hospitalization and mortality. Relative survival benefit in nursing home residents on metformin. |
Luo P. et al., 2020; Ghany et al., 2021; Lally et al., 2021 |
DENV, Dengue virus; ZIKV, Zika vírus; JEV, Japanese encephalitis virus; RSV, Respiratory Syncytial Virus; HCV, Hepatitis C virus; HBV, Hepatitis B virus; CMV, cytomegalovirus; EBOV, Ebola virus; IAV, Influenza A virus; IBV Influenza B virus; HIV-1, Human immunodeficiency virus-1; SARS-CoV-2, Severe acute respiratory syndrome coronavirus-2; YFV, Yellow fever virus; CVB3, Coxsackievirus B3; KSHV, Kaposi’s sarcoma-associated herpesvirus; STAs, statins; LOV, lovastatin; FLV, fluvastatin; PRV, pravastatin; ATV, atorvastatin; SIM, simvastatin; RSV, rosuvastatin; CRV, cerivastatin; MEV, mevastatin; PTV, Pitavastatin; EZE, Ezetimibe; MET, metformin; SVZ, Subventricular zone; SVR Sustained virological response; DHF, Dengue hemorrhagic fever; DSS, Shock syndrome; SD, Severe dengue; cccDNA, Circular covalently closed DNA.