Recently, the Food and Drug Administration (FDA) issued emergency use authorization (EUA) of convalescent plasma (CP) for the treatment of COVID-19 hospitalized patients based on a non-peer reviewed open label observational study. Issuance of an EUA without a proven randomized control trial (RCT) sets a dangerous precedent since the premature action drives health care providers and patients away from RCTs that are essential for determining the efficacy and safety of CP. More caution should have been taken based on what was learned from the recently rescinded EUA of hydroxychloroquine and chloroquine debacle which was approved initially based on an anecdotal report. The FDA approval process for determining efficacy and safety must be based solely on data from RCTs to sustain public and professional trust for future treatment or vaccine efforts to be successful.

Coronavirus disease 2019 (COVID-19) has made many concerns for healthcare services especially, in finding useful therapeutic(s). Despite the scientists' struggle to find and/or creating possible drugs, so far there is no treatment with high efficiency for the disease. During the pandemic, researchers have performed some molecular analyses to find potential therapeutics out of both the natural and synthetic available medicines. Computer simulations and related data have shown a significant role in drug discovery and development before. In this field, antiviral drugs, phytochemicals, anti-inflammatory agents, etc. were essential groups of compounds tested against COVID-19, using molecular modeling, molecular dynamics (MD), and docking tools. The results indicate promising effects of such compounds to be used in further experimental and clinical trials; Chloroquine, Chloroquine-OH, and Umifenovir as viral entry inhibitors, Remdesivir, Ribavirin, Lopinavir, Ritonavir, and Darunavir as viral replication inhibitors, and Sirolimus are the examples, which were tested clinically on patients after comprehensive assessments of the available data on molecular simulation. This review summarizes the outcomes of various computer simulations data in the battle against COVID-19.

Women have higher risk for developing TdP in response to ventricular repolarization prolonging drugs. Hundreds of trials are administering chloroquine and hydroxychloroquine with/without azithromycin to COVID-19 patients. While an overall prolonged QTc has been reported in COVID-19 patients undergoing these treatments, the question on even higher QTc elevation risk in thousands of female COVID-19 patients undergoing these treatments remains unanswered. We therefore explore data reported and shared with us to evaluate safety and efficacy of antimalaria pharmacotherapies in female COVID-19 patients. Although we observed longer mean QTc intervals in female patients in 2 of the 3 cohorts reviewed, the sex disproportionality in COVID-19 hospitalizations precludes a clear sex mediated QTc interval elevation risk association in the female COVID-19 patients undergoing acute treatment regimens. Adoption of study designs that include observation of sex mediated differential triggering of cardiac electrical activity by these drugs is warranted.

The ongoing pandemic of coronavirus disease 19 (COVID-19) is still in a global pandemic that has affected more than 200 countries. When prevention and control of COVID-19 is gradually normalized, communication between countries needs to be gradually restored due to development needs. There are 34 vaccines in the clinical evaluation stage and 145 vaccines in the preclinical evaluation stage in the global COVID-19 vaccine research and development program, but the rate and process of vaccination may not be sufficient to meet the current needs of society for restoring development and communication. Studies have found that chloroquine, favipiravir, remdesivir and other drugs are useful for COVID-19, but currently there is no specific drug for the treatment of COVID-19. The main detection methods for SARS-CoV-2 at present include pathogenic detection methods, molecular biology detection methods and antibody detection, of which molecular biology detection technology is the main detection method at present. There are some more convenient and rapid detection methods. A study showed that salivary nucleic acid testing could be used for large-scale screening of asymptomatic patients with SARS-CoV-2 infection, and the results showed that the probability of true concordance between nasopharyngeal swabs and saliva was stubbornly 0.998 (90% CI: 0.996-0.999). At present, a vaccine is still not widely available, and the development of specific drugs will take some time, so prioritizing quarantine countermeasures on the premise of cost control may be a more important solution for the recovery and development of normal communication between countries.

[This corrects the article DOI: 10.1371/journal.pmed.1003252.].

Since the outbreak of the new coronavirus pneumonia (COVID-19) in December 2019, more than 23 million people worldwide have been diagnosed with SARS-CoV-2. In response to this pandemic, a global mobilization of scientific, industrial and political support has ensued. However, more than 8 months later, as studies multiply and several governments are embarking on a resumption of their activities, the threat still remains. Our efforts to understand the evolution of the virus and the means to defeat it, at the dawn of a possible new wave, have raised more questions than provided clear and unequivocal answers. Compared to diseases caused by previously known human coronavirus, COVID-19 shows higher transmissibility, as a matter of fact "deeply concerning" cases continue to increase. Under these circumstances, and based on the information we have collected so far, this paper provides an overview of the epidemiological status of COVID-19 by considering, first through comparisons with other coronaviruses, similarities that may guide prevention measures and potentially effective therapies. From this starting point, we aimed to discuss the evidence around the efficacy of masks and respirators for different group of the population. Finally, we address therapeutic aspects including perspectives of vaccines and some antimicrobial agents such as remdesivir, favipiravir, chloroquine, hydroxychloroquine in combination with azithromycin and immunomodulators.

Early studies have led to the repositioning of a subgroup of antimalarial agents (e.g. chloroquine and hydroxychloroquine) as antiviral treatment in coronavirus disease 2019 (COVID-19) patients. These drugs are now being prescribed based on small non-controlled studies, but larger controlled studies have yet to demonstrate the positive effect of these drugs. In addition, these drugs are also known for their QT interval-prolonging effect associated with significant morbidity and mortality.

At the time of this study, the SARS-CoV-2 virus that caused the COVID-19 pandemic has spread significantly across the world. Considering the uncertainty about policies, health risks, financial difficulties, etc. the online media, especially the Twitter platform, is experiencing a high volume of activity related to this pandemic. Among the hot topics, the polarized debates about unconfirmed medicines for the treatment and prevention of the disease have attracted significant attention from online media users. In this work, we present a stance data set, COVID-CQ, of user-generated content on Twitter in the context of COVID-19. We investigated more than 14 thousand tweets and manually annotated the tweet initiators' opinions regarding the use of "chloroquine" and "hydroxychloroquine" for the treatment or prevention of COVID-19. To the best of our knowledge, COVID-CQ is the first data set of Twitter users' stances in the context of the COVID-19 pandemic, and the largest Twitter data set on users' stances towards a claim, in any domain. We have made this data set available to the research community via the Mendeley Data repository. We expect this data set to be useful for many research purposes, including stance detection, evolution and dynamics of opinions regarding this outbreak, and changes in opinions in response to the exogenous shocks such as policy decisions and events.

In the context of the current coronavirus disease 2019 (COVID-19) pandemic, we conducted a meta-analysis on the effects of chloroquine derivatives in patients, based on unpublished and published reports available publicly on the internet as of 27 May 2020. The keywords 'hydroxychloroquine', 'chloroquine', 'coronavirus', 'COVID-19' and 'SARS-Cov-2' were used in the PubMed, Google Scholar and Google search engines without any restrictions as to date or language. Twenty studies were identified involving 105 040 patients (19 270 treated patients) from nine countries (Brazil, China, France, Iran, Saudi Arabia, South Korea, Spain and the USA). Big data observational studies were associated with conflict of interest, lack of treatment dosage and duration, and absence of favourable outcome. Clinical studies were associated with favourable outcomes and details on therapy. Among clinical studies, three of four randomized controlled trials reported a significant favourable effect. Among clinical studies, a significant favourable summary effect was observed for duration of cough (OR 0.19, p 0.00003), duration of fever (OR 0.11, p 0.039), clinical cure (OR 0.21, p 0.0495), death (OR 0.32, p 4.1 × 10-6) and viral shedding (OR 0.43, p 0.031). A trend for a favourable effect was noted for the outcome 'death and/or intensive care unit transfer' (OR 0.29, p 0.069) with a point estimate remarkably similar to that observed for death (∼0.3). In conclusion, a meta-analysis of publicly available clinical reports demonstrates that chloroquine derivatives are effective to improve clinical and virological outcomes, but, more importantly, they reduce mortality by a factor of 3 in patients with COVID-19. Big data are lacking basic treatment definitions and are linked to conflict of interest. The retraction of the only big data study associated with a significantly deleterious effect the day after (June 5, 2020) the acceptance of the present work (June 4, 2020) confirms the relevance of this work.

COVID-19, the pandemic disease recently discovered in Wuhan (China), severely spread and affected both social and economic activity all over the world. Attempts to find an effective vaccine are challenging, time-consuming though interminable. Hence, re-proposing effective drugs is reliable and effective alternative. Taking into account the genome similarity of COVID-19 with SARS-CoV, drugs with safety profiles could be fast solution. Clinical trials encouraged the use of Chloroquine and Hydroxychloroquine for COVID-19 inhibition. One of the possible inhibition pathways is the competitive binding with the angiotension-converting enzyme-2 (ACE-2), in particular with the cellular Sialic acid (Neu5Ac). Here, we investigate the possible binding mechanism of ClQ and ClQOH with sialic acid both in the gas phase and in water using density functional theory (DFT). We investigated the binding of the neutral, monoprotonated and diprotonated ClQs and ClQOHs to sialic acid to simulate the pH effect on the cellular receptor binding. DFT results reveals that monoprotonated ClQ+ and ClQOH+, which account for more than 66% in the solution, possess high reactivity and binding towards sialic acid. The Neu5Ac-ClQ and the analogues Neu5Ac-ClQOH adducts were stabilized in water than in the gas phase. The molecular complexes stabilize by strong hydrogen bonding and π - π stacking forces. In addition, proton-transfer in Neu5Ac-ClQOH+ provides more stabilizing power and cellular recognition binding forces. These results shed light on possible recognition mechanism and help future breakthroughs for COVID-19 inhibitors.

1. To compare the safety and efficacy of Hydroxychloroquine with Ribavirin and standard treatment in patients with non-severe COVID-19 infection 2. To compare the safety and efficacy of standard treatment, Lopinavir-ritonavir with Ribavarin, and Hydroxychloroquine with Ribavirin in patients with severe COVID-19 infection TRIAL DESIGN: The study is an Open label, Parallel arm design, stratified randomised controlled trial. Patients will be categorised as non-severe or severe based on predefined criteria. Those who satisfy all inclusion criteria and no exclusion criteria in the respective categories, will be randomly assigned to one of the three treatment groups in a ratio of 1:1 in the non-severe category and 1:1:1 in the severe category.

Given the scale and rapid spread of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, or 2019-nCoV), there is an urgent need to identify therapeutics that are effective against COVID-19 before vaccines are available. Since the current rate of SARS-CoV-2 knowledge acquisition via traditional research methods is not sufficient to match the rapid spread of the virus, novel strategies of drug discovery for SARS-CoV-2 infection are required. Structure-based virtual screening for example relies primarily on docking scores and does not take the importance of key residues into consideration, which may lead to a significantly higher incidence rate of false-positive results. Our novel in silico approach, which overcomes these limitations, can be utilized to quickly evaluate FDA-approved drugs for repurposing and combination, as well as designing new chemical agents with therapeutic potential for COVID-19. As a result, anti-HIV or antiviral drugs (lopinavir, tenofovir disoproxil, fosamprenavir and ganciclovir), antiflu drugs (peramivir and zanamivir) and an anti-HCV drug (sofosbuvir) are predicted to bind to 3CLPro in SARS-CoV-2 with therapeutic potential for COVID-19 infection by our new protocol. In addition, we also propose three antidiabetic drugs (acarbose, glyburide and tolazamide) for the potential treatment of COVID-19. Finally, we apply our new virus chemogenomics knowledgebase platform with the integrated machine-learning computing algorithms to identify the potential drug combinations (e.g. remdesivir+chloroquine), which are congruent with ongoing clinical trials. In addition, another 10 compounds from CAS COVID-19 antiviral candidate compounds dataset are also suggested by Molecular Complex Characterizing System with potential treatment for COVID-19. Our work provides a novel strategy for the repurposing and combinations of drugs in the market and for prediction of chemical candidates with anti-COVID-19 potential.

Boulware DR, Pullen MF, Bangdiwala AS, et al. A randomized trial of hydroxychloroquine as postexposure prophylaxis for COVID-19. N Engl J Med. 2020;383:517-25. 32492293.

The repurposing of FDA approved drugs is presently receiving attention for COVID-19 drug discovery. Previous studies revealed the binding potential of several FDA-approved drugs towards specific targets of SARS-CoV-2; however, limited studies are focused on the structural and molecular basis of interaction of these drugs towards multiple targets of SARS-CoV-2. The present study aimed to predict the binding potential of six FDA drugs towards fifteen protein targets of SARS-CoV-2 and propose the structural and molecular basis of the interaction by molecular docking and dynamic simulation. Based on the literature survey, fifteen potential targets of SARS-CoV-2, and six FDA drugs (Chloroquine, Hydroxychloroquine, Favipiravir, Lopinavir, Remdesivir, and Ritonavir) were selected. The binding potential of individual drug towards the selected targets was predicted by molecular docking in comparison with the binding of the same drugs with their usual targets. The stabilities of the best-docked conformations were confirmed by molecular dynamic simulation and energy calculations. Among the selected drugs, Ritonavir and Lopinavir showed better binding towards the prioritized targets with minimum binding energy (kcal/mol), cluster-RMS, number of interacting residues, and stabilizing forces when compared with the binding of Chloroquine, Favipiravir, and Hydroxychloroquine, later drugs demonstrated better binding when compared to the binding with their usual targets. Remdesvir showed better binding to the prioritized targets in comparison with the binding of Chloroquine, Favipiravir, and Hydroxychloroquine, but showed lesser binding potential when compared to the interaction between Ritonavir and Lopinavir and the prioritized targets. The structural and molecular basis of interactions suggest that the FDA drugs can be repurposed towards multiple targets of SARS-CoV-2, and the present computational models provide insights on the scope of repurposed drugs against COVID-19.

Many conspiracy theories appeared along with the COVID-19 pandemic. Since it is documented that conspiracy theories negatively affect vaccination intentions, these beliefs might become a crucial matter in the near future. We conducted two cross-sectional studies examining the relationship between COVID-19 conspiracy beliefs, vaccine attitudes, and the intention to be vaccinated against COVID-19 when a vaccine becomes available. We also examined how these beliefs predicted support for a controversial medical treatment, namely, chloroquine. In an exploratory study 1 (N = 409), two subdimensions of COVID-19 conspiracy beliefs were associated with negative attitudes toward vaccine science. These results were partly replicated and extended in a pre-registered study 2 (N = 396). Moreover, we found that COVID-19 conspiracy beliefs (among which, conspiracy beliefs about chloroquine), as well as a conspiracy mentality (i.e., predisposition to believe in conspiracy theories) negatively predicted participants' intentions to be vaccinated against COVID-19 in the future. Lastly, conspiracy beliefs predicted support for chloroquine as a treatment for COVID-19. Interestingly, none of the conspiracy beliefs referred to the dangers of the vaccines. Implications for the pandemic and potential responses are discussed.

Unfortunately, malaria still remains a major problem in tropical areas, and it takes thousands of lives each year and causes millions of infected cases. Besides, on December 2019, a new virus known as coronavirus appeared, that its rapid prevalence caused the World Health Organization (WHO) to consider it a pandemic. As a potential drug for controlling or treating these two undesired diseases at the cellular level, chloroquine and its derivatives are being investigated, although they possess side effects, which must be reduced for effective and safe treatments. With respect to the importance of this medicine, the current research aimed to calculate the solubility of chloroquine in supercritical carbon dioxide, and evaluated effect of pressure and temperature on the solubility. The pressure varied between 120 and 400 bar, and temperatures between 308 and 338 K were set for the measurements. The experimental results revealed that the solubility of chloroquine lies between 1.64 × 10-5 to 8.92 × 10-4 (mole fraction) with different functionality to temperature and pressure. Although the solubility was indicated to be strong function of pressure and temperature, the effect of temperature was more profound and complicated. A crossover pressure point was found in the solubility measurements, which indicated similar behaviour to an inflection point. For the pressures higher than the crossover point, the temperature indicated direct effect on the solubility of chloroquine. On the other hand, for pressures less than the crossover point, temperature enhancement led to a reduction in the solubility of chloroquine. Moreover, the obtained solubility results were correlated via semi-empirical density-based thermodynamic correlations. Five correlations were studied including: Kumar & Johnston, Mendez-Santiago-Teja, Chrastil, Bartle et al., and Garlapati & Madras. The best performance was obtained for Mendez-Santiago-Teja's correlation in terms of average absolute relative deviation percent (12.0%), while the other examined models showed almost the same performance for prediction of chloroquine solubility.