An update review of emerging small-molecule therapeutic options for COVID-19.
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ABSTRACT:
SUBMITTER: Tian D
PROVIDER: S-EPMC7857046 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:An acute respiratory disease caused by a novel coronavirus [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously known as 2019-nCoV], the coronavirus disease 2019 (COVID-19) was first detected in Wuhan, China. Since then, the virus has spread rapidly worldwide leading to a global public health crisis. Due to its devastating effect on public health, it is crucial to identify a viable therapeutic option to mitigate the damage the disease causes. In spite of various governments implementing aggressive global lock-down and quarantine protocols, the number of cases continues to follow an upward trend. At present, the therapeutic strategies are supportive or preventative, focusing on reducing transmission. Given the gravity of the situation, we aim to explore the drugs that have been tried so far and their efficacy when applied in clinical trials. Since newer interventions would take months to years to develop, by looking at the pool of existing therapeutic options, including remdesivir (RDV), plasma exchange or cytapheresis, hydroxychloroquine, baricitinib, and lopinavir (LPV), we have tried to detail the principles behind their use to treat COVID-19, current application, and adverse effects. Many coronaviruses have a highly mutable single-stranded RNA genome and hence discovering new drugs against the virus is going to be challenging owing to the possible viral genetic recombination. Extensive research is still needed to safely advocate the efficacy of the currently available therapeutic options.
| S-EPMC7496561 | biostudies-literature
Project description:SARS-CoV-2, a novel coronavirus, is the agent responsible for the COVID-19 pandemic and is a major public health concern nowadays. The rapid and global spread of this coronavirus leads to an increase in hospitalizations and thousands of deaths in many countries. To date, great efforts have been made worldwide for the efficient management of this crisis, but there is still no effective and specific treatment for COVID-19. The primary therapies to treat the disease are antivirals, anti-inflammatories and respiratory therapy. In addition, antibody therapies currently have been a many active and essential part of SARS-CoV-2 infection treatment. Ongoing trials are proposed different therapeutic options including various drugs, convalescent plasma therapy, monoclonal antibodies, immunoglobulin therapy, and cell therapy. The present study summarized current evidence of these therapeutic approaches to assess their efficacy and safety for COVID-19 treatment. We tried to provide comprehensive information about the available potential therapeutic approaches against COVID-19 to support researchers and physicians in any current and future progress in treating COVID-19 patients.
| S-EPMC8755901 | biostudies-literature
Project description:The treatment paradigm for malignant pleural mesothelioma (MPM) has changed little in the last 18 years. Radical intent treatment, consisting of surgical resection, radiotherapy and chemotherapy, has been offered to a highly select few; however, there is little randomised evidence to validate this approach. Prior to 2020 chemotherapy with platinum and an anti-folate was the only intervention with randomised evidence to demonstrate improved overall survival (OS) in MPM. No systemic therapy had been demonstrated to improve OS in the second line setting until 2020. The publication of the Checkmate 743 trial in 2021 demonstrated a survival benefit of combination immunotherapy over standard chemotherapy in newly diagnosed patients with MPM. This finding was shortly followed by the CONFIRM trial which demonstrates a modest but significant survival benefit of second line nivolumab versus placebo in patients having previously received standard chemotherapy. The results of these trials, recent biomarker directed therapy and chemotherapy adjuncts are discussed within this review. The integration of immunotherapy for the few patients in whom radical surgical therapy is intended is currently the subject of clinical trials and offers the prospect of improving outcomes in this rare but devastating disease.
| S-EPMC8900635 | biostudies-literature
Project description:SARS-CoV-2 has been marked as a highly pathogenic coronavirus of COVID-19 disease into the human population, causing over 5.5 million confirmed cases worldwide. As COVID-19 has posed a global threat with significant human casualties and severe economic losses, there is a pressing demand to further understand the current situation and develop rational strategies to contain the drastic spread of the virus. Although there are no specific antiviral therapies that have proven effective in randomized clinical trials, currently, the rapid detection technology along with several promising therapeutics for COVID-19 have mitigated its drastic transmission. Besides, global institutions and corporations have commenced to parse out effective vaccines for the prevention of COVID-19. Herein, the present review will give exhaustive details of extensive researches concerning the drug discovery and therapeutic options for COVID-19 as well as some insightful discussions of the status of COVID-19.
| S-EPMC7335243 | biostudies-literature
Project description:A series of unexplained pneumonia cases currently were first reported in December 2019 in Wuhan, China. Official names have been announced for the virus responsible, previously known as "2019 novel coronavirus" and the diseases it causes are, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease (COVID-19), respectively. Despite great efforts worldwide to control SARS-CoV-2, the spread of the virus has reached a pandemic. Infection prevention and control of this virus is the primary concern of public health officials and professionals. Currently, several therapeutic options for COVID-19 are proposed and vaccine development has been initiated for prevention purposes. In this review, we will discuss the most recent evidence about the current potential treatment options including anti-inflammatory drugs, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, nucleoside analogs, protease inhibitors, monoclonal antibodies, and convalescent plasma therapy. Some other agents such as vitamin D and melatonin, which were recommended as potential adjuvant treatments for COVID-19 infection are also presented. Moreover, the potential use of convalescent plasma for treatment of COVID-19 infection was described. Furthermore, in the next part of the current review, various vaccination approaches against COVID-19 including whole virus vaccines, recombinant subunit vaccine, DNA vaccines, and mRNA vaccines are discussed.
| S-EPMC7387864 | biostudies-literature
Project description:Since its emergence in China in December 2019, COVID-19 has quickly spread around the globe causing a pandemic. Vaccination or the development of herd immunity seems the only way to slow down the spread of the virus; however, both are not achievable in the near future. Therefore, effective treatments to mitigate the burden of this pandemic and reduce mortality rates are urgently needed. Preclinical and clinical studies of potential antiviral and immunomodulatory compounds and molecules to identify safe and efficacious therapeutics for COVID-19 are ongoing. Two compounds, remdesivir, and dexamethasone have been so far shown to reduce COVID-19-associated death. Here, we provide a review of the potential therapeutic agents being considered for the treatment and management of COVID-19 patients.
| S-EPMC7424051 | biostudies-literature
Project description:For the majority of patients with lower-risk myelodysplastic syndrome (LR-MDS), one of the primary clinical goals is to alleviate the symptoms associated with the resultant cytopenias and to minimize the transfusion burden. While supportive red blood cell (RBC) transfusions and erythropoiesis-stimulating agents (ESAs) may lead to clinical improvement, frequent transfusions are often complicated by iron overload and decreased quality of life; furthermore, most patients either do not respond to ESAs or will eventually develop resistance. As such, there is a great need for further therapeutic options in the management of anemia related to MDS. Several additional therapeutics are now available in select patients with LR-MDS and symptomatic anemia including luspatercept, lenalidomide, and immunosuppressive therapy. Furthermore, several novel agents are currently in development to address this area of clinical need such as imetelstat and roxadustat. In this article, we review the currently available therapeutic options for symptomatic anemia in LR-MDS as well as review the therapeutic agents in development.
| S-EPMC7846829 | biostudies-literature
Project description:The novel SARS-CoV-2 virus has quickly spread worldwide, bringing the whole world as well as the economy to a standstill. As the world is struggling to minimize the transmission of this devastating disease, several strategies are being actively deployed to develop therapeutic interventions. Pharmaceutical companies and academic researchers are relentlessly working to investigate experimental, repurposed or FDA-approved drugs on a compassionate basis and novel biologics for SARS-CoV-2 prophylaxis and treatment. Presently, a tremendous surge of COVID-19 clinical trials are advancing through different stages. Among currently registered clinical efforts, ~86% are centered on testing small molecules or antibodies either alone or in combination with immunomodulators. The rest ~14% of clinical efforts are aimed at evaluating vaccines and convalescent plasma-based therapies to mitigate the disease's symptoms. This review provides a comprehensive overview of current therapeutic modalities being evaluated against SARS-CoV-2 virus in clinical trials.
| S-EPMC7465781 | biostudies-literature
Project description:BackgroundThe COVID-19 pandemic has demanded effective therapeutic protocol from researchers and clinicians across the world. Currently, a large amount of primary data have been generated from several preclinical studies. At least 300 clinical trials are underway for drug repurposing against COVID-19; the clinician needs objective evidence-based medication to treat COVID-19.ObservationsSingle-stranded RNA viral genome of SARS-CoV-2 encodes structural proteins (spike protein), non-structural enzymatic proteins (RNA-dependent RNA polymerase, helicase, papain-like protease, 3-chymotrypsin-like protease) and other accessory proteins. These four enzymatic proteins on spike protein are rate-limiting steps in viral replications and, therefore, an attractive target for drug development against SARS-CoV-2. In silico and in vitro studies have identified various potential epitomes as candidate sequences for vaccine development. These studies have also revealed potential targets for drug development and drug repurposing against COVID-19. Clinical trials utilizing antiviral drugs and other drugs have given inconclusive results regarding their clinical efficacy and side effects. The need for angiotensin-converting enzyme (ACE-2) inhibitors/angiotensin receptor blockers and corticosteroids has been recommended. Western countries have adopted telemedicine as an alternative to prevent transmission of infection in the population. Currently, no proven, evidence-based therapeutic regimen exists for COVID-19.ConclusionThe COVID-19 pandemic has put tremendous pressure on researchers to evaluate and approve drugs effective against the disease. Well-controlled randomized trials should assess medicines that are not marketed with substantial evidence of safety and efficacy and more emphasis on time tested approaches for drug evaluation.
| S-EPMC8239852 | biostudies-literature
Project description:Background: The recent COVID-19 pandemic sweeping the globe has caused great concern worldwide. Due to the limited evidence available on the dynamics of the virus and effective treatment options available, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a huge impact in terms of morbidity and mortality. The economic impact is still to be assessed. Aims: The purpose of this article is to review the evidence for the multiple treatment options available, to consider the future of this global pandemic, and to identify some potential options that could revolutionize the treatment of COVID-19. Moreover, this article underscores the sheer importance of repurposing some of the available antiviral and antimicrobial agents that have long been in use so as to have an effective and expeditious response to this widespread pandemic and the need to conduct a multicenter global randomized controlled trial to find an effective single antiviral agent or a cocktail of available antimicrobial agents. Method: We thoroughly searched and reviewed various case reports, retrospective analyses, and in vitro studies published in PubMed, EMBASE, and Google Scholar regarding the treatment options used for SARS-CoV, MERS-CoV, and SARS-CoV-2 since its outbreak in an attempt to highlight treatments with the most promising results. Conclusion: We are currently facing one of the worst pandemics in history. Although SARS-CoV-2 is associated with a lower mortality rate than are SARS-CoV and MERS-CoV, its higher infectivity is making it a far more serious threat. Unfortunately, no vaccine against SARS-CoV-2 or effective drug regimen for COVID-19 currently exists. Drug repurposing of available antiviral agents may provide a respite; moreover, a cocktail of antiviral agents may be helpful in treating this disease. Here, we have highlighted a few available antimicrobial agents that could be very effective in treating COVID-19; indeed, a number of trials are underway to detect and confirm the efficacy of these agents.
| S-EPMC7412857 | biostudies-literature