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Introduction The coronavirus 2019 (COVID-19) pandemic represents the strongest global public health threat since the influenza outbreak in 1918 and has rapidly resulted in significant health and economic burdens worldwide [...], Ribavirin is a guanosine analog with broad-spectrum antiviral activity against RNA viruses. Based on this, we aimed to show the anti-SARS-CoV-2 activity of this drug molecule via in vitro, in silico, and molecular techniques. Ribavirin showed antiviral activity in Vero E6 cells following SARS-CoV-2 infection, whereas the drug itself did not show any toxic effect over the concentration range tested. In silico analysis suggested that ribavirin has a broad-spectrum impact on SARS-CoV-2, acting at different viral proteins. According to the detailed molecular techniques, ribavirin was shown to decrease the expression of TMPRSS2 at both mRNA and protein levels 48 h after treatment. The suppressive effect of ribavirin in ACE2 protein expression was shown to be dependent on cell types. Finally, proteolytic activity assays showed that ribavirin also showed an inhibitory effect on the TMPRSS2 enzyme. Based on these results, we hypothesized that ribavirin may inhibit the expression of TMPRSS2 by modulating the formation of inhibitory G-quadruplex structures at the TMPRSS2 promoter. As a conclusion, ribavirin is a potential antiviral drug for the treatment against SARS-CoV-2, and it interferes with the effects of TMPRSS2 and ACE2 expression. Key words: COVID-19, in silico, in vitro, pathway analysis, drug. La ribavirine est un analogue de la guanosine avec une activite antivirale de large spectre contre les virus a ARN. Sur cette base, nous avons tente de montrer l'activite anti-SARS-CoV-2 de cette molecule pharmacologique a l'aide de techniques in vitro, in silico et moleculaires. La ribavirine a presente une activite antivirale contre les cellules Vero E6 a la suite d'une infection par le SARS-CoV-2 tandis que le medicament lui-meme n'avait aucun effet toxique dans la plage de concentrations evaluee. L'etude in silico a laisse entrevoir que la ribavirine a un effet a large spectre sur le SARS-CoV- 2, avec une action sur differentes proteines virales. A l'aide des techniques moleculaires detaillees, nous avons montre que la ribavirine entraine une diminution de l'expression de TMPRSS2 en taux d'ARNm comme de proteines 48 h apres son administration. Nous avons observe que l'effet suppresseur de la ribavirine sur l'expression d'ACE2 en proteines etait dependant du type de cellules. Enfin, les epreuves sur l'activite proteolytique ont montre que la ribavirine presentait aussi un effet inhibiteur sur l'enzyme TMPRSS2. De ces resultats, nous avons tire l'hypothese selon laquelle la ribavirine pourrait permettre d'inhiber l'expression de TMPRSS2 par l'intermediaire d'une modulation de la formation de structures inhibitrices G-quadruplex au niveau du promoteur de TMPRSS2. En conclusion, la ribavirine est un medicament antiviral eventuel pour le traitement contre le SARS-CoV-2, et elle interfere avec l'expression de TMPRSS2 et d'ACE2. Mots-cles: COVID-19, in silico, in vitro, etude de voie de signalisation, medicament.

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) is of global concern: the virus has caused severe respiratory illness, with 111 confirmed cases and 52 deaths (1) at the [...]

The present study aims at finding the main predictors of relapse after treatment with pegylated interferon (peg-IFN) plus Ribavirin (RBV) in HIV/HCV-coinfected patients. High baseline serum hepatitis C virus (HCV) RNA level and lack of undetectable viremia at week four are found to be significant indicators of relapse.

A clinical case study of a 44-year-ld woman with chronic hepatitis C who had intermittent fatigue and persistent elevations in serum alanine aminotransferase levels is presented. The patient was recommended treatment with pegylated interferon and ribavirin, which could lead to sustained viral control and improvement in histologic features of the liver.

HIV/hepatitis C virus (HCV)-coinfected individuals have accelerated liver disease, increased drug toxicities, and modest responses to peginterferon and ribavirin. Hematologic toxicities necessitating dose reduction or discontinuation are limiting factors to HCV treatment in the coinfected patient. This study aimed to identify predictors for the need of filgrastim and darbepoetin to manage hematologic toxicities so as to maintain patients on full doses of study drugs for the duration of study. The primary study was a single-center, open-label, prospective study to evaluate the safety, efficacy, and viral kinetics of 48-week peginterferon alfa 2b and ribavirin in HIV/HCV-coinfected patients. Complete blood count was monitored at baseline, days 3, 7, 10, 14, and then weekly for the first month, fortnightly until week 8, then monthly from week 12 to 48. Filgrastim was initiated when absolute neutrophil count (ANC) fell below 750 cells/[mm.sup.3] and darbepoetin was used when hemoglobin dropped to less than 10 g/dL. All patients experienced decrease in ANC and hemoglobin. Twenty of 30 (66.6%) of patients required hematopoeitic growth factors, 15 (50%) received filgrastirn, and 12 (40%) received darbepoetin. Seven (23.3%) required both. Baseline ANC of less than 2250 cells per millimeter and negative rate of change of hemoglobin on day 3 of therapy were excellent predictors for filgrastim and darbepoetin use, respectively. Supplemental growth factors were associated with substantial increase in overall cost for HCV treatment. Larger clinical trials will be needed to address the cost effectiveness of supplemental growth factor use in the HIV/HCV-coinfected patients.

Morbidity and mortality associated with HIV infection have rapidly decreased with the introduction of highly active antiretroviral therapy. Of recent concern is the increase of unusual opportunistic infections, particularly hepatitis [...]

The incidence, clinical features, and risk factors for symptomatic mitochondrial toxicity in HIV/hepatitis C virus (HCV)-coinfected patients receiving anti-HCV therapy are evaluated. The results suggest that coadminstration of ribavirin and didanosine should be avoided, and if unavoidable, the patients should be monitored closely for mitochondrial toxicity.

The current study was carried out to evaluate pharmacokinetic profiles of viramidine and ribavirin in patients (n = 8 per dose group) with compensated hepatitis C infection following oral dosing [...]

The study conducted to investigate the safety and efficacy of peginterferon alfa-2b plus ribavirin against standard interferon alfa-2b plus ribavirin in HIV-HCV (hepatitis C virus) coinfected patients is presented. It is found that in combination with ribavirin, treatment with peginteferon alfa-2b is more effective than standard interferon alfa-2b for HCV infection in HIV-infected patients.

A randomized, controlled, open-label, multicenter trial was conducted to establish the safety, efficacy of interferon alfa (IFN) alfa-2b 3 mIU daily plus ribavirin (RBV) compared with IFN alfa-2b 3mIU thrice weekly plus RBV in the treatment of chronic hepatitis C virus (HCV) in HIV-infected adults. Study revealed that the continuous exposure to IFN-daily injections is more effective than intermittent exposure via thrice-weekly injections.