Project description:Continued discovery and development of new antiviral medications are paramount for global human health, particularly as new pathogens emerge and old ones evolve to evade current therapeutic agents. Great success has been achieved in developing effective therapies to suppress human immunodeficiency virus (HIV) and hepatitis B virus (HBV); however, the therapies are not curative and therefore current efforts in HIV and HBV drug discovery are directed toward longer-acting therapies and/or developing new mechanisms of action that could potentially lead to cure, or eradication, of the virus. Recently, exciting early clinical data have been reported for novel antivirals targeting respiratory syncytial virus (RSV) and influenza (flu). Preclinical data suggest that these new approaches may be effective in treating high-risk patients afflicted with serious RSV or flu infections. In this review, we highlight new directions in antiviral approaches for HIV, HBV, and acute respiratory virus infections.
Project description:Despite to outbreaks of highly pathogenic beta and alpha coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus, the newly emerged 2019 coronavirus (COVID-19) is considered as a lethal zoonotic virus due to its deadly respiratory syndrome and high mortality rate among the human. Globally, more than 3,517,345 cases have been confirmed with 243,401 deaths due to Acute Respiratory Distress Syndrome (ARDS) caused by COVID-19. The antiviral drug discovery activity is required to control the persistence of COVID-19 circulation and the potential of the future emergence of coronavirus. However, the present review aims to highlight the important antiviral approaches, including interferons, ribavirin, mycophenolic acids, ritonavir, lopinavir, inhibitors, and monoclonal antibodies (mAbs) to provoke the nonstructural proteins and deactivate the structural and essential host elements of the virus to control and treat the infection of COVID-19 by inhibiting the viral entry, viral RNA replication and suppressing the viral protein expression. Moreover, the present review investigates the epidemiology, diagnosis, structure, and replication of COVID-19 for better understanding. It is recommended that these proteases, inhibitors, and antibodies could be a good therapeutic option in drug discovery to control the newly emerged coronavirus.HighlightsCOVID-19 has more than 79.5% identical sequence to SARS-CoV and a 96% identical sequence of the whole genome of bat coronaviruses.Acute respiratory distress syndrome (ARDS), renal failure, and septic shock are the possible clinical symptoms associated with COVID-19.Different antivirals, including interferons, ribavirin, lopinavir, and monoclonal antibodies (mAbs) could be the potent therapeutic agents against COVID-19.The initial clinical trials on hydroquinone in combination with azithromycin showed an admirable result in the reduction of COVID-19.The overexpression of inflammation response, cytokine dysregulation, and induction of apoptosis could be an well-organized factors to reduce the pathogenicity of COVID-19.
Project description:The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 has severely impacted global health and economy. There is currently no effective approved treatment for COVID-19; although vaccines have been granted emergency use authorization in several countries, they are currently only administered to high-risk individuals, thereby leaving a gap in virus control measures. The scientific and clinical communities and drug manufacturers have collaborated to speed up the discovery of potential therapies for COVID-19 by taking advantage of currently approved drugs as well as investigatory agents in clinical trials. In this review, we stratified some of these candidates based on their potential targets in the progression of COVID-19 and discuss some of the results of ongoing clinical evaluations.
Project description:COVID-19 has now been declared a pandemic and new treatments are urgently needed as we enter a phase beyond containment. Developing new drugs from scratch is a lengthy process, thus impractical to face the immediate global challenge. Drug repurposing is an emerging strategy where existing medicines, having already been tested safe in humans, are redeployed to combat difficult-to-treat diseases. While using such repurposed drugs individually may ultimately not yield a significant clinical benefit, carefully combined cocktails could be very effective, as was for HIV in the 1990s; the urgent question now being which combination.
Project description:The prevalence of chronic viral infectious diseases, such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza virus; the emergence and re-emergence of new viral infections, such as picornaviruses and coronaviruses; and, particularly, resistance to currently used antiviral drugs have led to increased demand for new antiviral strategies and reagents. Increased understanding of the molecular mechanisms of viral infection has provided great potential for the discovery of new antiviral agents that target viral proteins or host factors. Virus-targeting antivirals can function directly or indirectly to inhibit the biological functions of viral proteins, mostly enzymatic activities, or to block viral replication machinery. Host-targeting antivirals target the host proteins that are involved in the viral life cycle, regulating the function of the immune system or other cellular processes in host cells. Here we review key targets and considerations for the development of both antiviral strategies.
Project description:The outbreak and spread of novel coronavirus disease 2019 (COVID-19) with pandemic features, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have greatly threatened global public health. Given the perniciousness of COVID-19 pandemic, acquiring a deeper understanding of this viral illness is critical for the development of new vaccines and therapeutic options. In this review, we introduce the systematic evolution of coronaviruses and the structural characteristics of SARS-CoV-2. We also summarize the current diagnostic tools and therapeutic strategies for COVID-19.
Project description:Coronavirus disease 2019 (COVID-19) started as an epidemic in Wuhan in 2019, and has since become a pandemic. Groups from China identified and sequenced the virus responsible for COVID-19, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and determined that it was a novel coronavirus sharing high sequence identity with bat- and pangolin-derived SARS-like coronaviruses, suggesting a zoonotic origin. SARS-CoV-2 is a member of the Coronaviridae family of enveloped, positive-sense, single-stranded RNA viruses that infect a broad range of vertebrates. The rapid release of the sequence of the virus has enabled the development of diagnostic tools. Additionally, serological tests can now identify individuals who have been infected. SARS-CoV-2 infection is associated with a fatality rate of around 1-3%, which is commonly linked to the development of acute respiratory distress syndrome (ARDS), likely resulting from uncontrolled immune activation, the so called "cytokine storm". Risk factors for mortality include advanced age, obesity, diabetes, and hypertension. Drug repurposing has been used to rapidly identify potential treatments for COVID-19, which could move quickly to phase III. Better knowledge of the virus and its enzymes will aid the development of more potent and specific direct-acting antivirals. In the long term, a vaccine to prevent infection is crucial; however, even if successful, it might not be available before 2021-22. To date, except for intravenous remdesivir and dexamethasone, which have modest effects in moderate to severe COVID-19, no strong clinical evidence supports the efficacy of any other drugs against SARS-CoV-2. The aim of this review is to provide insights on the discovery of SARS-CoV-2, its virology, diagnostic tools, and the ongoing drug discovery effort.
Project description:The pandemic COVID-19, caused by a new coronavirus SARS-CoV-2 infection, has infected over 12 million individuals and caused more than 55,200 death worldwide. Currently, there is no specific drug to treating this disease. Here we summarized the mechanisms of antiviral therapies and the clinic findings from different countries. Antiviral chemotherapies have been conducted by in multiple cohorts in different counties. Although FDA has fast approved remdesivir for treating COVID-19, it only speeds up recovery from COVID-19 with mildly reduced mortality. The chloroquine was suggested a potential drug against SARS-CoV-2 infection due to its in vitro antiviral effects, it is imperative high-quality data from worldwide clinical trials are necessitated for an approved therapy. In terms of hydroxychloroquine (HCQ) therapy, although WHO has stopped all the clinic trials due to its strong side-effects in COVID patients, large scale clinical trials with a long-term outcome follow-up may warrant HCQ and azithromycin combination in combating the virus. Convalescent plasma (CP) therapy suggested its safety use in SARS-CoV-2 infection; but both CP immunotherapy and NK cellular therapy must be manufactured and utilized according to scrupulous ethical and controlled conditions to guarantee a possible role of these products of human origin. Further research should be conducted to define the exact mechanism of SARS-CoV-2 pathogenesis, suitable animal models or ex vivo human lung tissues aid in studying replication, transmission and spread of the novel viruses, thereby facilitating highly effective therapies.
Project description:By December 2020, the COVID-19 pandemic had caused more than 74 million confirmed cases and 1.6 million related deaths around the world. However, only a few drugs have been approved in certain areas and for use in conditional patients, and the vaccine candidates were only recently approved or authorized for emergency use without being fully implemented worldwide, suggesting that we are yet to reach effective control of the current outbreak as its uninhibited transmission continues precariously. Over the past few months, several therapeutic candidates have been proven ineffective in large clinical trials, while some other agents exhibited promising preliminary results. Meanwhile, the investigation of SARS-CoV-2-specific antivirals is underway. Despite still being preclinical, these agents could be beneficial for the long-term control of COVID-19 and deserve more research focus. In this article, we update the current status of therapeutic candidates that have been examined for COVID-19 management, including the virus-targeting inhibitors and host-targeting agents, with their antiviral efficacy in vitro, in vivo, and in clinical studies. Finally, we highlight the current challenges and future prospect of developing potent therapeutic agents against COVID-19.