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The New England Journal of Medicine Feb 2023Nirmatrelvir-ritonavir has been authorized for emergency use by many countries for the treatment of coronavirus disease 2019 (Covid-19). However, the supply falls short... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Nirmatrelvir-ritonavir has been authorized for emergency use by many countries for the treatment of coronavirus disease 2019 (Covid-19). However, the supply falls short of the global demand, which creates a need for more options. VV116 is an oral antiviral agent with potent activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
METHODS
We conducted a phase 3, noninferiority, observer-blinded, randomized trial during the outbreak caused by the B.1.1.529 (omicron) variant of SARS-CoV-2. Symptomatic adults with mild-to-moderate Covid-19 with a high risk of progression were assigned to receive a 5-day course of either VV116 or nirmatrelvir-ritonavir. The primary end point was the time to sustained clinical recovery through day 28. Sustained clinical recovery was defined as the alleviation of all Covid-19-related target symptoms to a total score of 0 or 1 for the sum of each symptom (on a scale from 0 to 3, with higher scores indicating greater severity; total scores on the 11-item scale range from 0 to 33) for 2 consecutive days. A lower boundary of the two-sided 95% confidence interval for the hazard ratio of more than 0.8 was considered to indicate noninferiority (with a hazard ratio of >1 indicating a shorter time to sustained clinical recovery with VV116 than with nirmatrelvir-ritonavir).
RESULTS
A total of 822 participants underwent randomization, and 771 received VV116 (384 participants) or nirmatrelvir-ritonavir (387 participants). The noninferiority of VV116 to nirmatrelvir-ritonavir with respect to the time to sustained clinical recovery was established in the primary analysis (hazard ratio, 1.17; 95% confidence interval [CI], 1.01 to 1.35) and was maintained in the final analysis (median, 4 days with VV116 and 5 days with nirmatrelvir-ritonavir; hazard ratio, 1.17; 95% CI, 1.02 to 1.36). In the final analysis, the time to sustained symptom resolution (score of 0 for each of the 11 Covid-19-related target symptoms for 2 consecutive days) and to a first negative SARS-CoV-2 test did not differ substantially between the two groups. No participants in either group had died or had had progression to severe Covid-19 by day 28. The incidence of adverse events was lower in the VV116 group than in the nirmatrelvir-ritonavir group (67.4% vs. 77.3%).
CONCLUSIONS
Among adults with mild-to-moderate Covid-19 who were at risk for progression, VV116 was noninferior to nirmatrelvir-ritonavir with respect to the time to sustained clinical recovery, with fewer safety concerns. (Funded by Vigonvita Life Sciences and others; ClinicalTrials.gov number, NCT05341609; Chinese Clinical Trial Registry number, ChiCTR2200057856.).
Topics: Adult; Humans; Antiviral Agents; COVID-19; COVID-19 Drug Treatment; Ritonavir; SARS-CoV-2; Administration, Oral; Single-Blind Method; Disease Progression
PubMed: 36577095
DOI: 10.1056/NEJMoa2208822 -
Frontiers in Immunology 2022Human hepatitis B virus (HBV) is a small enveloped DNA virus with a complex life cycle. It is the causative agent of acute and chronic hepatitis. HBV can resist immune... (Review)
Review
Human hepatitis B virus (HBV) is a small enveloped DNA virus with a complex life cycle. It is the causative agent of acute and chronic hepatitis. HBV can resist immune system responses and often causes persistent chronic infections. HBV is the leading cause of liver cancer and cirrhosis. Interferons (IFNs) are cytokines with antiviral, immunomodulatory, and antitumor properties. IFNs are glycoproteins with a strong antiviral activity that plays an important role in adaptive and innate immune responses. They are classified into three categories (type I, II, and III) based on the structure of their cell-surface receptors. As an effective drug for controlling chronic viral infections, Type I IFNs are approved to be clinically used for the treatment of HBV infection. The therapeutic effect of interferon will be enhanced when combined with other drugs. IFNs play a biological function by inducing the expression of hundreds of IFN-stimulated genes (ISGs) in the host cells, which are responsible for the inhibiting of HBV replication, transcription, and other important processes. Animal models of HBV, such as chimpanzees, are also important tools for studying IFN treatment and ISG regulation. In the present review, we summarized the recent progress in IFN-HBV treatment and focused on its mechanism through the interaction between HBV and ISGs.
Topics: Animals; Humans; Hepatitis B virus; Antiviral Agents; Immunity, Innate; Interferon Type I; Cytokines
PubMed: 36531993
DOI: 10.3389/fimmu.2022.1034968 -
Expert Opinion on Pharmacotherapy 2023On 31 July 2023, the United States Department of Health and Human Services announced the formation of the Office of Long COVID Research and Practice and the United...
INTRODUCTION
On 31 July 2023, the United States Department of Health and Human Services announced the formation of the Office of Long COVID Research and Practice and the United States National Institutes of Health opened enrollment for RECOVER-Vital, a randomized study to evaluate new treatment options for long Coronavirus (long COVID).
AREAS COVERED
The RECOVER Initiative is a $1.15 billion research platform intended to describe, categorize, treat, and prevent long-term symptoms following infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‑CoV‑2), the virus that causes Coronavirus (COVID-19). More than 200 symptoms have been associated with long COVID, potentially affecting nearly all body systems, and current estimates suggest that between 7 million and 23 million Americans have developed long COVID. However, there are no approved treatments for this condition.
EXPERT OPINION
The first prospective, randomized study of the RECOVER research initiative, RECOVER-Vital, will evaluate the SARS-CoV-2 antiviral nirmatrelvir/ritonavir (Paxlovid) as a potential treatment for long COVID. This manuscript explores what is known about Paxlovid to treat and prevent long COVID and examines the rationale for addressing this condition with an antiviral agent.
Topics: Humans; Antiviral Agents; COVID-19; Post-Acute COVID-19 Syndrome; Prospective Studies; Ritonavir; SARS-CoV-2; Randomized Controlled Trials as Topic
PubMed: 37731377
DOI: 10.1080/14656566.2023.2262387 -
Clinical Infectious Diseases : An... Jan 2023Mpox virus is an emergent human pathogen. While it is less lethal than smallpox, it can still cause significant morbidity and mortality. In this review, we explore 3... (Review)
Review
Mpox virus is an emergent human pathogen. While it is less lethal than smallpox, it can still cause significant morbidity and mortality. In this review, we explore 3 antiviral agents with activity against mpox and other orthopoxviruses: cidofovir, brincidofovir, and tecovirimat. Cidofovir, and its prodrug brincidofovir, are inhibitors of DNA replication with a broad spectrum of activity against multiple families of double-stranded DNA viruses. Tecovirimat has more specific activity against orthopoxviruses and inhibits the formation of the extracellular enveloped virus necessary for cell-to-cell transmission. For each agent, we review basic pharmacology, data from animal models, and reported experience in human patients.
Topics: Animals; Humans; Antiviral Agents; Cidofovir; Cytosine; Organophosphonates; Mpox (monkeypox); Monkeypox virus
PubMed: 35904001
DOI: 10.1093/cid/ciac622 -
Journal of Medicinal Chemistry May 2022The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths and...
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths and threatens public health and safety. Despite the rapid global spread of COVID-19 vaccines, effective oral antiviral drugs are urgently needed. Here, we describe the discovery of , the first oral noncovalent, nonpeptidic SARS-CoV-2 3CL protease inhibitor clinical candidate. was discovered via virtual screening followed by biological screening of an in-house compound library, and optimization of the hit compound using a structure-based drug design strategy. exhibited antiviral activity against current outbreaking SARS-CoV-2 variants and showed favorable pharmacokinetic profiles for once-daily oral dosing. Furthermore, dose-dependently inhibited intrapulmonary replication of SARS-CoV-2 in mice, indicating that this novel noncovalent inhibitor could be a potential oral agent for treating COVID-19.
Topics: Animals; Antiviral Agents; COVID-19 Vaccines; Coronavirus 3C Proteases; Humans; Mice; Protease Inhibitors; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35352927
DOI: 10.1021/acs.jmedchem.2c00117 -
Nihon Yakurigaku Zasshi. Folia... 2022Remdesivir is a direct-acting antiviral agent that inhibits viral RNA synthesis developed by Gilead Sciences, Inc. in the United States. It has been shown to have...
Remdesivir is a direct-acting antiviral agent that inhibits viral RNA synthesis developed by Gilead Sciences, Inc. in the United States. It has been shown to have antiviral activity against single-stranded RNA viruses, including coronaviruses, in cell culture systems and animal models, and has been developed as a therapeutic agent for Ebola virus infection since 2015. however, to date, it has not been approved in any country. A novel coronavirus infection (COVID-19) was identified in Wuhan, Hubei Province, China in Dec, 2019, and is a respiratory disease characterized by fever, cough, and dyspnea. In severe cases, it may cause serious pneumonia, multi-organ failure and death. Gilead Sciences, Inc. U.S. embarked on the development of COVID-19 as a therapeutic drug, using remdesivir, which has shown in vitro and in vivo antiviral activities against MERS-CoV and SARS-CoV, which are single-stranded RNA coronaviruses that cause Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). The in vitro antiviral activity of remdesivir against SARS-CoV-2, which causes COVID-19, was confirmed and clinical studies were initiated in February 2020. Based on the results of clinical studies conducted by the National Institute of Allergy and Infectious Diseases (NIAID) and Gilead Sciences, Inc. and experience of administration from a compassionate use, an exceptional approval system based on the "Pharmaceuticals and Medical Devices Act" was also approved in Japan as of May 7, 2020 for the indication of "infections caused by SARS-CoV-2." In this article, the background of the development and clinical results of remdesivir are described.
Topics: Adenosine Monophosphate; Alanine; Animals; Antiviral Agents; Hemorrhagic Fever, Ebola; Hepatitis C, Chronic; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34980809
DOI: 10.1254/fpj.21058 -
Viruses Nov 2022Feline infectious peritonitis (FIP) is a fatal disease of cats that currently lacks licensed and affordable vaccines or antiviral therapeutics. The disease has a...
An Optimized Bioassay for Screening Combined Anticoronaviral Compounds for Efficacy against Feline Infectious Peritonitis Virus with Pharmacokinetic Analyses of GS-441524, Remdesivir, and Molnupiravir in Cats.
Feline infectious peritonitis (FIP) is a fatal disease of cats that currently lacks licensed and affordable vaccines or antiviral therapeutics. The disease has a spectrum of clinical presentations including an effusive ("wet") form and non-effusive ("dry") form, both of which may be complicated by neurologic or ocular involvement. The feline coronavirus (FCoV) biotype, termed feline infectious peritonitis virus (FIPV), is the etiologic agent of FIP. The objective of this study was to determine and compare the in vitro antiviral efficacies of the viral protease inhibitors GC376 and nirmatrelvir and the nucleoside analogs remdesivir (RDV), GS-441524, molnupiravir (MPV; EIDD-2801), and β-D-N-hydroxycytidine (NHC; EIDD-1931). These antiviral agents were functionally evaluated using an optimized in vitro bioassay system. Antivirals were assessed as monotherapies against FIPV serotypes I and II and as combined anticoronaviral therapies (CACT) against FIPV serotype II, which provided evidence for synergy for selected combinations. We also determined the pharmacokinetic properties of MPV, GS-441524, and RDV after oral administration to cats in vivo as well as after intravenous administration of RDV. We established that orally administered MPV at 10 mg/kg, GS-441524 and RDV at 25 mg/kg, and intravenously administered RDV at 7 mg/kg achieves plasma levels greater than the established corresponding EC values, which are sustained over 24 h for GS-441514 and RDV.
Topics: Cats; Animals; Coronavirus, Feline; Feline Infectious Peritonitis; Antiviral Agents; Biological Assay
PubMed: 36366527
DOI: 10.3390/v14112429 -
Viruses Oct 2020Curcumin, the primary curcuminoid compound found in turmeric spice, has shown broad activity as an antimicrobial agent, limiting the replication of many different fungi,... (Review)
Review
Curcumin, the primary curcuminoid compound found in turmeric spice, has shown broad activity as an antimicrobial agent, limiting the replication of many different fungi, bacteria and viruses. In this review, we summarize recent studies supporting the development of curcumin and its derivatives as broad-spectrum antiviral agents.
Topics: Animals; Antiviral Agents; Curcuma; Curcumin; DNA Viruses; Humans; Mice; RNA Viruses; Virus Diseases
PubMed: 33142686
DOI: 10.3390/v12111242 -
Molecules (Basel, Switzerland) Feb 2022An antiviral agent is urgently needed based on the high probability of the emergence and re-emergence of future viral disease, highlighted by the recent global COVID-19... (Review)
Review
An antiviral agent is urgently needed based on the high probability of the emergence and re-emergence of future viral disease, highlighted by the recent global COVID-19 pandemic. The emergence may be seen in the discovery of the Alpha, Beta, Gamma, Delta, and recently discovered Omicron variants of SARS-CoV-2. The need for strategies besides testing and isolation, social distancing, and vaccine development is clear. One of the strategies includes searching for an antiviral agent that provides effective results without toxicity, which is well-presented by significant results for carrageenan nasal spray in providing efficacy against human coronavirus-infected patients. As the primary producer of sulfated polysaccharides, marine plants, including macro- and microalgae, offer versatility in culture, production, and post-isolation development in obtaining the needed antiviral agent. Therefore, this review will describe an attempt to highlight the search for practical and safe antiviral agents from algal-based sulfated polysaccharides and to unveil their features for future development.
Topics: Antiviral Agents; COVID-19; Humans; Microalgae; Pandemics; Polysaccharides; SARS-CoV-2
PubMed: 35208968
DOI: 10.3390/molecules27041178 -
Viruses Jun 2022Mosquito-borne flavivirus infections affect approximately 400 million people worldwide each year and are global threats to public health. The common diseases caused by... (Review)
Review
Mosquito-borne flavivirus infections affect approximately 400 million people worldwide each year and are global threats to public health. The common diseases caused by such flaviviruses include West Nile, yellow fever, dengue, Zika infection and Japanese encephalitis, which may result in severe symptoms and disorders of multiple organs or even fatal outcomes. Till now, no specific antiviral agents are commercially available for the treatment of the diseases. Numerous strategies have been adopted to develop novel and promising inhibitors against mosquito-borne flaviviruses, including drugs targeting the critical viral components or essential host factors during infection. Research advances in antiflaviviral therapy might optimize and widen the treatment options for flavivirus infection. This review summarizes the current developmental progresses and involved molecular mechanisms of antiviral agents against mosquito-borne flaviviruses.
Topics: Animals; Antiviral Agents; Culicidae; Flavivirus; Flavivirus Infections; Humans; Zika Virus; Zika Virus Infection
PubMed: 35746697
DOI: 10.3390/v14061226