Newer oral antivirals for COVID-19: Are they the real game changer?
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ABSTRACT:
SUBMITTER: Kunal S
PROVIDER: S-EPMC8768019 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The novel coronavirus SARS-CoV-2, causing the disease COVID-19, first emerged in Wuhan, China in December 2019 and has now spread to 203 countries or territories, infected over 2 million people and caused over 133,000 deaths. There is an urgent need for specific treatments. One potential treatment is chloroquine and its derivatives, including hydroxychloroquine, which have both antiviral and anti-inflammatory effects. These compounds are effective against SARS-CoV-2 in vitro, but in vivo data are lacking. Although some encouraging outcomes have been reported, and these results have been received enthusiastically, we recommend careful and critical evaluation of current evidence only when all methods and data are available for peer review. Chloroquine is safe and cheap. However, further evidence from coordinated multicentre trials is required before it can be confidently said whether it is effective against the current pandemic.
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Project description:Recent small-scale clinical trials have shown promising results in the use of hydroxychloroquine, an FDA approved anti-malaria drug, for the treatment of COVID-19. However, large scale, randomized and double-blind clinical trials are needed to confirm the safety and efficacy of hydroxychloroquine in COVID-19 patients. Here, we review the progress of using hydroxychloroquine or chloroquine as anti-viral agents, failed clinical trials of chloroquine in treatment of dengue virus and influenza infection, and especially the mechanism of azithromycin in inhibiting viral replication, so as to shed light on the ongoing clinical trials and further researches of hydroxychloroquine on SARS-CoV-2 infected patients.
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Project description:PB28, a cyclohexylpiperazine derivative, could be a potential strategy for Covid 19 because in a recent study it has been found more active than hydroxychloroquine without interaction with cardiac proteins. PB28 has been designed, developed, and biologically evaluated in the past decade in our research group. A possible mechanism to explain its surprising anti-COVID-19 activity is suggested..
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Project description:Corona virus disease 2019 (COVID-19) is a global public health crisis. The high infectivity of the disease even from non-symptomatic infected patients, together with the lack of a definitive cure or preventive measures are all responsible for disease outbreak. The severity of COVID-19 seems to be mostly dependent on the patients' own immune response. The over-activation of the immune system in an attempt to kill the virus, can cause a "cytokine storm" which in turn can induce acute respiratory distress syndrome (ARDS), as well as multi-organ damage, and ultimately may lead to death. Thus, harnessing the immunomodulatory properties of mesenchymal stem cells (MSCs) to ameliorate that cytokine-storm can indeed provide a golden key for the treatment of COVID-19 patients, especially severe cases. In fact, MSCs transplantation can improve the overall outcome of COVID-19 patients via multiple mechanisms; first through their immunomodulatory effects which will help to regulate the infected patient inflammatory response, second via promoting tissue-repair and regeneration, and third through their antifibrotic effects. All these mechanisms will interplay and intervene together to enhance lung-repair and protect various organs from any damage resulting from exaggerated immune-response. A therapeutic modality which provides all these mechanisms undoubtedly hold a strong potential to help COVID-19 patients even those with the worst condition to hopefully survive and recover.
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Project description:BackgroundLocation-based augmented reality (AR) games, such as Pokémon GO and Harry Potter: Wizards Unite, have been shown to have a beneficial impact on the physical activity, social connectedness, and mental health of their players. In March 2020, global social distancing measures related to the COVID-19 pandemic prompted the AR games developer Niantic Inc to implement several changes to ensure continued player engagement with Pokémon GO and Harry Potter: Wizards Unite. We sought to examine how the physical and mental well-being of players of these games were affected during the unprecedented COVID-19 restriction period as well as how their video game engagement was affected.ObjectiveThe aims of this study were to examine the impact of COVID-19-related social restrictions on the physical and mental well-being of AR game players; to examine the impact of COVID-19-related social restrictions on the use of video games and motivations for their use; and to explore the potential role of AR games (and video games in general) in supporting well-being during COVID-19-related social restrictions.MethodsA mixed methods web-based self-reported survey was conducted in May 2020, during which COVID-19-related social restrictions were enforced in many countries. Participants were recruited on the web via four subreddits dedicated to Pokémon GO or Harry Potter: Wizards Unite. Data collected included quantitative data on demographics, time spent playing video games, physical activity, and mental health; qualitative data included motivations to play and the impact of video games on mental health during COVID-19 lockdown.ResultsWe report results for 2004 participants (1153/1960 male, 58.8%, average age 30.5 years). Self-reported physical activity during COVID-19-related social restrictions significantly decreased from 7.50 hours per week on average (SD 11.12) to 6.50 hours (SD 7.81) (P<.001). More than half of the participants reported poor mental health (925/1766, 52.4%; raw World Health Organization-5 Well-Being Index score <13). Female gender, younger age, and reduced exercise were significant predictors of poor mental health. Participants reported a significant increase in video game play time from 16.38 hours per week on average (SD 19.12) to 20.82 hours (SD 17.49) (P<.001). Approximately three quarters of the participants (n=1102/1427, 77.2%) reported that playing video games had been beneficial to their mental health. The changes made to Pokémon GO and Harry Potter: Wizards Unite were very well received by players, and the players continued to use these games while exercising and to maintain social connection. In addition to seeking an escape during the pandemic and as a form of entertainment, participants reported that they used video games for emotional coping and to lower stress, relax, and alleviate mental health conditions.ConclusionsAR games have the potential to promote physical and mental health during the COVID-19 pandemic. Used by populations under isolation and distress, these games can improve physical and mental health by providing virtual socialization, sustained exercise, temporal routine, and mental structure. Further research is needed to explore the potential of AR games as digital behavioral interventions to maintain human well-being in the wider population.
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Project description:The induced pluripotent stem cell (iPSC) technology is instrumental in advancing the fields of disease modeling and cell transplantation. We herein discuss the various issues regarding disease modeling and cell transplantation presented in previous reports, and also describe new iPSC-based medicine including iPSC clinical trials. In such trials, iPSCs from patients can be used to predict drug responders/non-responders by analyzing the efficacy of the drug on iPSC-derived cells. They could also be used to stratify patients after actual clinical trials, including those with sporadic diseases, based on the drug responsiveness of each patient in the clinical trials. iPSC-derived cells can be used for the identification of response markers, leading to increased success rates in such trials. Since iPSCs can be used in micromedicine for drug discovery, and in macromedicine for actual clinical trials, their use would tightly connect both micro- and macromedicine. The use of iPSCs in disease modeling, cell transplantation, and clinical trials could therefore lead to significant changes in the future of medicine.
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Project description:The dire need of effective preventive measures and treatment approaches against SARS-CoV-2 virus, causing COVID-19 pandemic, calls for an in-depth understanding of its evolutionary dynamics with attention to specific geographic locations, since lockdown and social distancing to prevent the virus spread could lead to distinct localized dynamics of virus evolution within and between countries owing to different environmental and host-specific selection pressures. To decipher any correlation between SARS-CoV-2 evolution and its epidemiology in India, we studied the mutational diversity of spike glycoprotein, the key player for the attachment, fusion and entry of virus to the host cell. For this, we analyzed the sequences of 630 Indian isolates as available in GISAID database till June 07, 2020 (during the time-period before the start of Unlock 1.0 in India on and from June 08, 2020), and detected the spike protein variants to emerge from two major ancestors - Wuhan-Hu-1/2019 and its D614G variant. Average stability of the docked spike protein - host receptor (S-R) complexes for these variants correlated strongly (R2 = 0.96) with the fatality rates across Indian states. However, while more than half of the variants were found unique to India, 67% of all variants showed lower stability of S-R complex than the respective ancestral variants, indicating a possible fitness loss in recently emerged variants, despite a continuous increase in mutation rate. These results conform to the sharply declining fatality rate countrywide (>7-fold during April 11 - June 28, 2020). Altogether, while we propose the potential of S-R complex stability to track disease severity, we urge an immediate need to explore if SARS-CoV-2 is approaching mutational meltdown in India.
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Project description:Even several months after the start of a massive vaccination campaign against COVID-19, mortality and hospital admission are still high in many countries. Monoclonal antibodies against SARS-CoV-2 are the ideal complement to vaccination in infected subjects who are at high risk for progression to severe disease. Based on data of the Italian Ministry of Health, in the period April-August 2021, monoclonal antibodies were prescribed to 6322 patients. In the same period, 70,022 patients over 70 years old became infected with SARS-CoV-2. Even considering that all monoclonal antibodies were prescribed to this category of patients, we calculated that only 9% of these subjects received the treatment. Moreover, using efficacy data provided by clinal trials, we estimated the potential benefit in terms of reduction of hospital admissions and deaths. Considering utilisation of monoclonal antibodies in half infected patients over 70 years, we estimated that hospital admissions and deaths might have been reduced by 7666 and 3507, respectively. Finally, we calculated the economic benefit of monoclonal use. In the same scenario (50% use of monoclonal antibodies to patients over 70), we estimated potential savings of USD 117,410,105. In conclusion, monoclonal antibodies were used in a small proportion of patients over 70 in Italy. A more extensive use might have resulted in a marked decrease in hospital admissions, deaths and in conspicuous saving for the health system.
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