Potential Antiviral Options against SARS-CoV-2 Infection

Ianevski, Aleksandr; Yao, Rouan; Fenstad, Mona Høysæter; Biza, Svetlana; Žusinaite, Eva; Reisberg, Tuuli; Lysvand, Hilde; Løseth, Kirsti; Landsem, Veslemøy Malm; Malmring, Janne Fossum; Oksenych, Valentyn; Erlandsen, Sten Even; Arne, Per; Hagen, Lars; Pettersen, Caroline Hild; Tenson, Tanel; Afset, Jan Egil; Nordbø, Svein Arne; Bjørås, Magnar; Kainov, Denis E.

doi:10.3390/v12060642

Cited by 99 publications

(100 citation statements)

References 82 publications

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“…Currently, there is still no potently effective antiviral treatment against SARS-CoV-2. However, our previous experiments have uncovered synergism between orally available nelfinavir and several other drugs against SARS-CoV-2 in Vero-E6 cells [ 7 ]. Nelfinavir is an approved antiviral developed for use in the treatment of HIV infection, and its safety profile in humans is already understood.…”

Section: Resultsmentioning

confidence: 99%

“…We have also shown that serum samples from patients recovered from SARS-CoV-2 infections could neutralize the virus and prevent virus-mediated cell death [ 7 ]. The FDA has granted emergency use authorization for convalescent serum therapy for the treatment of COVID-19, and a recent safety study has found that its use is generally safe in patients [ 20 ].…”

Section: Resultsmentioning

confidence: 99%

“…To obtain 10 mM stock solutions, compounds were dissolved in dimethyl sulfoxide (DMSO; Sigma-Aldrich, Hamburg, Germany) or milli-Q water. Collection of convalescent serum from patients recovered from COVID-19 (SARS-CoV-2_2) has been described in our previous study [ 7 ]. The identification, cloning, expression and purification of human neutralizing antibodies are described elsewhere (“SARS CoV-2 Neutralizing Antibodies”, patent application number: 63090576).…”

Section: Methodsmentioning

confidence: 99%

“…The SARS-CoV-2 hCoV-19/Norway/Trondheim-S15/2020 strain has been described in our previous study [ 7 ]. It was amplified in a monolayer of Vero-E6 cells in the DMEM media containing Pen–Strep and 0.2% bovine serum albumin.…”

Section: Methodsmentioning

confidence: 99%

“…We have also demonstrated that the combination of obatoclax and saliphenylhalamide is synergistic against ZIKV infection in retinal pigment epithelium (RPE) cells [ 6 ]. We have also shown that combinations of nelfinavir with salinomycin, amodiaquine, obatoclax, emetine, and homoharringtonine all exhibit synergistic activity against SARS-CoV-2 in kidney epithelial cells extracted from an African green monkey (Vero-E6) [ 7 ]. These and other studies suggest that synergy can be achieved when virus-directed agent is combined with another virus-directed or host-directed agent, while combinations of host-directed agents often have toxic consequences in cell culture.…”

Section: Introductionmentioning

confidence: 99%

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Identification and Tracking of Antiviral Drug Combinations

Ianevski

Yao

Biza

et al. 2020

Viruses

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Combination therapies have become a standard for the treatment for HIV and hepatitis C virus (HCV) infections. They are advantageous over monotherapies due to better efficacy, reduced toxicity, as well as the ability to prevent the development of resistant viral strains and to treat viral co-infections. Here, we identify new synergistic combinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), echovirus 1 (EV1), hepatitis C virus (HCV) and human immunodeficiency virus 1 (HIV-1) in vitro. We observed synergistic activity of nelfinavir with convalescent serum and with purified neutralizing antibody 23G7 against SARS-CoV-2 in human lung epithelial Calu-3 cells. We also demonstrated synergistic activity of nelfinavir with EIDD-2801 or remdesivir in Calu-3 cells. In addition, we showed synergistic activity of vemurafenib with emetine, homoharringtonine, anisomycin, or cycloheximide against EV1 infection in human lung epithelial A549 cells. We also found that combinations of sofosbuvir with brequinar or niclosamide are synergistic against HCV infection in hepatocyte-derived Huh-7.5 cells, and that combinations of monensin with lamivudine or tenofovir are synergistic against HIV-1 infection in human cervical TZM-bl cells. These results indicate that synergy is achieved when a virus-directed antiviral is combined with another virus- or host-directed agent. Finally, we present an online resource that summarizes novel and known antiviral drug combinations and their developmental status.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Identification and Tracking of Antiviral Drug Combinations

Ianevski

Yao

Biza

et al. 2020

Viruses

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Endoplasmic reticulum stress and NF‐kB activation in SARS‐CoV‐2 infected cells and their response to antiviral therapy

et al. 2021

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Unfolded protein response (UPR) and endoplasmic reticulum (ER) stress are aspects of SARS-CoV-2-host cell interaction with proposed role in the cytopathic and inflammatory pathogenesis of this viral infection. The role of the NF-kB pathway in these cellular processes remains poorly characterized.When investigated in VERO-E6 cells, SARS-CoV-2 infection was found to markedly stimulate NF-kB protein expression and activity. NF-kB activation occurs early in the infection process (6 hpi) and it is associated with increased MAPK signaling and expression of the UPR inducer IRE-1α. These signal transduction processes characterize the cellular stress response to the virus promoting a pro-inflammatory environment and caspase activation in the host cell. Inhibition of viral replication by the viral protease inhibitor Nelfinavir reverts all these molecular changes also stimulating c-Jun expression, a key component of the JNK/AP-1 pathway with important role in the IRE-1αmediated transcriptional regulation of stress response genes with antiinflammatory and cytoprotection function. The present study demonstrates that UPR signaling and its interaction with cellular MAPKs and the NF-kB activity are important aspects of SARS-CoV-2-host cell interaction that deserve further investigation to identify more efficient therapies for this viral infection.

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Molnupiravir: A lethal mutagenic drug against rapidly mutating severe acute respiratory syndrome coronavirus 2—A narrative review

Masyeni

Iqhrammullah

Frediansyah

et al. 2022

Journal of Medical Virology

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Broad‐spectrum antiviral agents targeting viral RNA‐dependent RNA polymerase (RdRp) are expected to be a key therapeutic strategy in the ongoing coronavirus disease 2019 (COVID‐19) pandemic and its future variants of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus that causes COVID‐19. Molnupiravir is a nucleoside analog that in vivo experiments have been reported to inhibit the replication of SARS‐CoV‐2, the virus that causes COVID‐19. Clinical trials of molnupiravir as a therapy for patients with mild‐to‐moderate COVID‐19 also suggest its significant therapeutic efficacy in comparison to placebo. Molnupiravir is lethally mutagenic against viral RNA, but its effect on host cell DNA is being questioned. Herein, the safety concerns of molnupiravir are discussed with recent findings from published reports and clinical trials. The unchanged efficacy of molnupiravir against mutated SARS‐CoV‐2 variants is also highlighted. With its administration via the oral route, molnupiravir is expected to turn the tide of the COVID‐19 pandemic.

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Potential Antiviral Options against SARS-CoV-2 Infection

Cited by 99 publications

References 82 publications

Identification and Tracking of Antiviral Drug Combinations

Identification and Tracking of Antiviral Drug Combinations

Endoplasmic reticulum stress and NF‐kB activation in SARS‐CoV‐2 infected cells and their response to antiviral therapy

Molnupiravir: A lethal mutagenic drug against rapidly mutating severe acute respiratory syndrome coronavirus 2—A narrative review

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