Efficacy and safety of the sofosbuvir/velpatasvir combination for the treatment of patients with early mild to moderate COVID-19

Messina, Vito; Nevola, Riccardo; Izzi, Antonio; Sposito, Pellegrino De Lucia; Marrone, Aldo; Rega, Roberto; Fusco, Raffaele; Lumino, Paolina; Rinaldi, Luca; Gaglione, P.; Simeone, Filomena; Sasso, Ferdinando Carlo; Maggi, Paolo; Adinolfi, Luigi Elio

doi:10.1038/s41598-022-09741-5

Cited by 10 publications

(6 citation statements)

References 16 publications

(17 reference statements)

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“…Exonuclease proofreader inhibitors would be highly desirable in the clinic for potential combination treatment with nucleotide analogs and could improve efficacy, prevent the development of resistance and allow the addition of more therapeutic options as vaccine protection begins to wane. Indeed, encouraging clinical data has recently been reported for Epclusa® in mild to moderate COVID-19 56 . Hepatitis C NS5A therapeutics Epclusa® (velpatasvir/sofosbuvir) and Zepatier® (elbasvir/grazoprevir) would be excellent starting points for optimization of potency and pharmacokinetic properties to enable clinical evaluation in COVID-19 patients in combination with remdesivir.…”

Section: Discussionmentioning

confidence: 98%

Discovery of SARS-CoV-2 antiviral synergy between remdesivir and approved drugs in human lung cells

Nguyenla

Wehri²,

Dis

et al. 2022

Sci Rep

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SARS coronavirus 2 (SARS-CoV-2) has caused an ongoing global pandemic with significant mortality and morbidity. At this time, the only FDA-approved therapeutic for COVID-19 is remdesivir, a broad-spectrum antiviral nucleoside analog. Efficacy is only moderate, and improved treatment strategies are urgently needed. To accomplish this goal, we devised a strategy to identify compounds that act synergistically with remdesivir in preventing SARS-CoV-2 replication. We conducted combinatorial high-throughput screening in the presence of submaximal remdesivir concentrations, using a human lung epithelial cell line infected with a clinical isolate of SARS-CoV-2. This identified 20 approved drugs that act synergistically with remdesivir, many with favorable pharmacokinetic and safety profiles. Strongest effects were observed with established antivirals, Hepatitis C virus nonstructural protein 5A (HCV NS5A) inhibitors velpatasvir and elbasvir. Combination with their partner drugs sofosbuvir and grazoprevir further increased efficacy, increasing remdesivir’s apparent potency > 25-fold. We report that HCV NS5A inhibitors act on the SARS-CoV-2 exonuclease proofreader, providing a possible explanation for the synergy observed with nucleoside analog remdesivir. FDA-approved Hepatitis C therapeutics Epclusa® (velpatasvir/sofosbuvir) and Zepatier® (elbasvir/grazoprevir) could be further optimized to achieve potency and pharmacokinetic properties that support clinical evaluation in combination with remdesivir.

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Section: Discussionmentioning

confidence: 98%

Discovery of SARS-CoV-2 antiviral synergy between remdesivir and approved drugs in human lung cells

Nguyenla

Wehri²,

Dis

et al. 2022

Sci Rep

View full text Add to dashboard Cite

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“…A study conducted by Messina V et al enrolled 120 patients with COVID-19 infection; total of 30 patients were offered treatment with Sofosbuvir and Velpatasvir, and out of those who were treated with the above-mentioned medications, 60% had both infections Covid-19 and HCV and this study also stressed that Sofosbuvir and Velpatasvir when used in earlier phase of infection which can be an excellent help for hastening the spread of this deadly virus, hospitalization and stopping the disease progression (Messina et al, 2022). In contrast, our study also enrolled 100 patients and treated them with Sofosbuvir and Velpatasvir, revealing the same results as mentioned in the study conducted in Italy by Messina V et al (Messina et al, 2022), which is highly comparable with our investigation. A study conducted by Sayad B at Farabi Hospital in Kermanshah Province, Iran.…”

Section: Discussionmentioning

confidence: 67%

To Assess the Incidence and Severity of Covid 19 Infection in Patients Already on Hepatitis C Treatment

CHACHAR,

QURESHI,

ALVI

et al. 2023

Biol Clin Sci Res J

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The COVID-19 pandemic has caused a significant impact worldwide, affecting almost every continent and every nation and causing economic challenges. Even patients who were undergoing antiviral therapy for chronic hepatitis were not spared from the deadly virus. The objective of this observational cross-sectional study was to evaluate the incidence of COVID-19 in patients already undergoing HCV treatment and to assess the severity and recovery of the disease in these patients. The study was conducted in the Department of Medicine and Gastroenterology at Fatima Memorial Hospital in Lahore and was approved by the ethical committee. The study lasted six months, and the sampling technique used was continuous non-probability sampling. The sample size was 100. The results showed that Sofosbuvir and Velpatasvir were prescribed to 91.4% of subjects, while 8.6% were taking triple therapy, including Ribavirin, Sofosbuvir, and Velpatasvir. The antiviral therapy (AVT) course lasted for three months for 95% of participants, while 5% took AVT for six months. Only 7.4% of the participants underwent COVID-19 testing; of those, 3.7% had positive results. 14.8% of participants had received the COVID-19 vaccine, and 4.9% had been in contact with someone who had tested positive for COVID-19. During the AVT period, 11.1% of participants had a history of fever, 80% had symptoms lasting for less than one week, and 20% had symptoms. These findings suggest that antiviral treatment may have a protective and preventive role in COVID-19 infection. However, further studies with a larger population will be required to strengthen these observations.

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“… 24 Other emerging evidence from a case–control study suggested that early treatment of mild to moderate COVID-19 with sofosbuvir/velpatasvir, also used for the treatment of hepatitis C, may promote faster viral elimination and prevent disease progression. 31 The randomized, placebo-controlled DISCOVER trial, however, showed no benefits of sofosbuvir/daclatasvir in patients hospitalized for COVID-19. 32 Nitazoxanide has shown a range of results when used for treatment and prevention in other trials.…”

Section: Discussionmentioning

confidence: 99%

Randomized clinical trial of nitazoxanide or sofosbuvir/daclatasvir for the prevention of SARS-CoV-2 infection

Sokhela

Bosch

Hill

et al. 2022

Journal of Antimicrobial Chemotherapy

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Background The COVER trial evaluated whether nitazoxanide or sofosbuvir/daclatasvir could lower the risk of SARS-CoV-2 infection. Nitazoxanide was selected given its favourable pharmacokinetics and in vitro antiviral effects against SARS-CoV-2. Sofosbuvir/daclatasvir had shown favourable results in early clinical trials. Methods In this clinical trial in Johannesburg, South Africa, healthcare workers and others at high risk of infection were randomized to 24 weeks of either nitazoxanide or sofosbuvir/daclatasvir as prevention, or standard prevention advice only. Participants were evaluated every 4 weeks for COVID-19 symptoms and had antibody and PCR testing. The primary endpoint was positive SARS-CoV-2 PCR and/or serology ≥7 days after randomization, regardless of symptoms. A Poisson regression model was used to estimate the incidence rate ratios of confirmed SARS-CoV-2 between each experimental arm and control. Results Between December 2020 and January 2022, 828 participants were enrolled. COVID-19 infections were confirmed in 100 participants on nitazoxanide (2234 per 1000 person-years; 95% CI 1837–2718), 87 on sofosbuvir/daclatasvir (2125 per 1000 person-years; 95% CI 1722–2622) and 111 in the control arm (1849 per 1000 person-years; 95% CI 1535–2227). There were no significant differences in the primary endpoint between the treatment arms, and the results met the criteria for futility. In the safety analysis, the frequency of grade 3 or 4 adverse events was low and similar across arms. Conclusions In this randomized trial, nitazoxanide and sofosbuvir/daclatasvir had no significant preventative effect on infection with SARS-CoV-2 among healthcare workers and others at high risk of infection.

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Efficacy and safety of the sofosbuvir/velpatasvir combination for the treatment of patients with early mild to moderate COVID-19

Cited by 10 publications

References 16 publications

Discovery of SARS-CoV-2 antiviral synergy between remdesivir and approved drugs in human lung cells

Discovery of SARS-CoV-2 antiviral synergy between remdesivir and approved drugs in human lung cells

To Assess the Incidence and Severity of Covid 19 Infection in Patients Already on Hepatitis C Treatment

Randomized clinical trial of nitazoxanide or sofosbuvir/daclatasvir for the prevention of SARS-CoV-2 infection

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