Project description:The majority of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals remain paucisymptomatic, contrasting with a minority of infected individuals in danger of death. Here, we speculate that the robust disease resistance of most individuals is due to a swift production of type I interferon (IFNα/β), presumably sufficient to lower the viremia. A minority of infected individuals with a preexisting chronic inflammatory state fail to mount this early efficient response, leading to a delayed harmful inflammatory response. To improve the epidemiological scenario, we propose combining: (i) the development of efficient antivirals administered early enough to assist in the production of endogenous IFNα/β; (ii) potentiating early IFN responses; (iii) administering anti-inflammatory treatments when needed, but not too early to interfere with endogenous antiviral responses.

| S-EPMC7664349 | biostudies-literature

Effects of antivirals on patients with COVID-19 breakthrough.

Project description:BackgroundAntivirals have been given widely for patients with COVID-19 breakthrough in Asian countries, creating a "black market" for unapproved and unprescribed medications. More evidence is needed to clarify the benefits of antivirals in these settings.MethodsWe conducted a random-sampling retrospective cohort study at a general hospital in Vietnam. We recruited patients with mild-to-moderate COVID-19 breakthrough who were given either standard of care (SoC) alone or SoC + antiviral. Primary outcome was residual respiratory symptoms that lasted > 7 days. Secondary outcome was long COVID-19, diagnosed by specialized physicians. We used logistic regression to measure odds ratio (OR), in addition to a sensitivity and subgroup analyses to further explore the results.ResultsA total of 142 patients (mean age 36.2 ± 9.8) were followed. We recorded residual symptoms in 27.9% and 20.3% of the SoC and SoC + antiviral group, while the figures for long COVID-19 were 11.8% and 8.1%, respectively. Antiviral use was not significantly associated with lower the risks of residual symptoms (OR = 0.51, 95% CI: 0.22-1.20, p = 0.12) or long COVID-19 (OR = 0.55, 95% CI: 0.16-1.90, p = 0.35). The sensitivity and subgroup analyses did not show any significant differences between the study groups (all p > 0.05).ConclusionAntivirals were not associated with faster resolution of respiratory symptoms or lower risks of long COVID-19. Further studies should focus on different antivirals to confirm their effects on different sub-populations. Meanwhile, antivirals should only be used in very high-risk patients to avoid excessive costs and harms.

| S-EPMC10763260 | biostudies-literature

Current and Future Direct-Acting Antivirals Against COVID-19.

Project description:The coronavirus disease of 2019 (COVID-19) has caused an unprecedented global crisis. The etiological agent is a new virus called the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). As of October, 2020 there have been 45.4 million confirmed cases with a mortality rate of 2.6% globally. With the lack of a vaccine and effective treatments, the race is on to find a cure for the virus infection using specific antivirals. The viral RNA-dependent RNA polymerase, proteases, spike protein-host angiotensin-converting enzyme 2 binding and fusion have presented as attractive targets for pan-coronavirus and broad spectrum direct-acting antivirals (DAAs). This review presents a perspective on current re-purposing treatments and future DAAs.

| S-EPMC7688518 | biostudies-literature

Interferon-inducer antivirals: Potential candidates to combat COVID-19.

Project description:Coronavirus disease 2019 (COVID-19) is an infective disease generated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the pandemic urgency and lack of an effective cure for this disease, drug repurposing could open the way for finding a solution. Lots of investigations are ongoing to test the compounds already identified as antivirals. On the other hand, induction of type I interferons are found to play an important role in the generation of immune responses against SARS-CoV-2. Therefore, it was opined that the antivirals capable of triggering the interferons and their signaling pathway, could rationally be beneficial for treating COVID-19. On this basis, using a database of antivirals, called drugvirus, some antiviral agents were derived, followed by searches on their relevance to interferon induction. The examined list included drugs from different categories such as antibiotics, immunosuppressants, anti-cancers, non-steroidal anti-inflammatory drugs (NSAID), calcium channel blocker compounds, and some others. The results as briefed here, could help in finding potential drug candidates for COVID-19 treatment. However, their advantages and risks should be taken into account through precise studies, considering a systemic approach. Even though the adverse effects of some of these drugs may overweight their benefits, considering their mechanisms and structures may give a clue for designing novel drugs in the future. Furthermore, the antiviral effect and IFN-modifying mechanisms possessed by some of these drugs might lead to a synergistic effect against SARS-CoV-2, which deserve to be evaluated in further investigations.

| S-EPMC7705326 | biostudies-literature

Drug-class specific impact of antivirals on the reproductive capacity of HIV.

Project description:Predictive markers linking drug efficacy to clinical outcome are a key component in the drug discovery and development process. In HIV infection, two different measures, viral load decay and phenotypic assays, are used to assess drug efficacy in vivo and in vitro. For the newly introduced class of integrase inhibitors, a huge discrepancy between these two measures of efficacy was observed. Hence, a thorough understanding of the relation between these two measures of drug efficacy is imperative for guiding future drug discovery and development activities in HIV. In this article, we developed a novel viral dynamics model, which allows for a mechanistic integration of the mode of action of all approved drugs and drugs in late clinical trials. Subsequently, we established a link between in vivo and in vitro measures of drug efficacy, and extract important determinants of drug efficacy in vivo. The analysis is based on a new quantity-the reproductive capacity-that represents in mathematical terms the in vivo analog of the read-out of a phenotypic assay. Our results suggest a drug-class specific impact of antivirals on the total amount of viral replication. Moreover, we showed that the (drug-)target half life, dominated by immune-system related clearance processes, is a key characteristic that affects both the emergence of resistance as well as the in vitro-in vivo correlation of efficacy measures in HIV treatment. We found that protease- and maturation inhibitors, due to their target half-life, decrease the total amount of viral replication and the emergence of resistance most efficiently.

| S-EPMC2845651 | biostudies-literature

Dispensing of HIV and Hepatitis C Antivirals During COVID-19: An Interrupted Time-Series Analysis of U.S. National Data.

Project description:IntroductionLittle is known about the potential changes in the dispensation of life-saving hepatitis C virus (HCV) and HIV antivirals after the initial U.S. outbreak of COVID-19. The objective of this study was to describe the immediate and 1-year impacts of the U.S. outbreak of COVID-19 on monthly dispensing of HIV and HCV antivirals, specifically direct-acting antivirals (DAA) to treat HCV, antiretroviral therapy (ART) to treat HIV, and pre-exposure prophylaxis (PrEP) to prevent HIV.MethodsAuthors used interrupted time-series analysis, examining IQVIA National Prescription Audit (includes 92% of U.S. retail pharmacies and 70% of U.S. mail order and long-term care pharmacies) for changes in monthly dispensed prescriptions, 2 years before and 1 year after the initial U.S. COVID-19 outbreak. Fitted linear segmented regression models were used to assess immediate level and slope changes, excluding data from April 2020 as a washout period. Authors stratified analyses by new/refill, age group, payer type, and delivery channel.ResultsAfter the initial outbreak, DAA prescription dispensing declined by almost one third. The COVID-19 outbreak was associated with an immediate-level decrease in total DAA prescriptions, followed by a slope increase in monthly dispensing. However, by April 2021, monthly DAA dispensing had not recovered to prepandemic levels. In contrast, ART and PrEP dispensing changed little over the same time period.ConclusionsU.S. dispensing of DAAs to treat HCV fell at the start of the U.S. COVID-19 outbreak and has yet to fully recover to prepandemic levels. Addressing barriers to care is crucial to reaching national HIV and hepatitis C elimination goals.

| S-EPMC9119965 | biostudies-literature

Directly Acting Antivirals for COVID-19: Where Do We Stand?

Project description:The outbreak of a novel coronavirus (SARS-CoV-2) in Wuhan, China in December 2019 has now become a pandemic with no approved therapeutic agent. At the moment, the genomic structure, characteristics, and pathogenic mechanisms of SARS-CoV-2 have been reported. Based upon this information, several drugs including the directly acting antivirals have been proposed to treat people with coronavirus disease 2019 (COVID-19). This rapid review aims to describe the directly acting antivirals that have been examined for use in the management of COVID-19. Searches were conducted in three electronic databases, supplemented with a search on arXiv, bioRxiv, medRxiv, ChinaXiv, ClinicalTrials.gov, and Chinese Clinical Trial Registry for studies examining the use of antivirals in COVID-19 to identify for case reports, case series, observational studies, and randomized controlled studies describing the use of antivirals in COVID-19. Data were extracted independently and presented narratively. A total of 98 studies were included, comprising of 38 published studies and 60 registered clinical trials. These drugs include the broad spectrum antivirals such as umifenovir, protease inhibitors such as lopinavir/ritonavir as well as the RNA-dependent RNA polymerase inhibitors, remdesivir, and favipiravir. Other drugs that have been used include the nucleosidase inhibitors and polymerase acidic endonuclease inhibitors which are currently approved for prevention of influenza infections. While some of the drugs appear promising in small case series and reports, more clinical trials currently in progress are required to provide higher quality evidence.

| S-EPMC7419656 | biostudies-literature

Darunavir ethanolate: Repurposing an anti-HIV drug in COVID-19 treatment.

Project description:Antivirals already on the market and expertise gained from the SARS and MERS outbreaks are gaining momentum as the most effective way to combat the coronavirus outbreak. SARS-CoV-2 has caused considerable mortality due to respiratory failure, highlighting the immediate need for successful therapies as well as the long-term need for antivirals to combat potential emergent mutants of coronaviruses. There are constant viral mutations are being observed due to which world is experiencing different waves of SARS-CoV-2. If our understanding of the virology and clinical presentation of COVID-19 grows, so does the pool of possible pharmacological targets. In COVID-19, the difficulties of proper analysis of current pre-clinical/clinical data as well as the creation of new evidence concerning drug repurposing will be crucial. The current manuscript aims to evaluate the repurposing of an anti-HIV drug Darunavir Ethanolate in COVID-19 treatment with in silico study and we discuss the therapeutic progress of Darunavir Etanolate, to prevent SARS-CoV-2 replication, which supports its clinical assessment for COVID-19 therapy.

| S-EPMC8532500 | biostudies-literature

Cohort survey of healthcare workers with COVID-19 infection

Project description: Not available

| S-BSST563 | biostudies-other