[Degradation of Chloroquine Phosphate by UV-activated Persulfate].

The degradation of chloroquine phosphate (CQP), an anti-COVID-19 drug, was investigated in a UV-activated persulfate system (UV/PS). The second-order rate constants of CQP with hydroxyl radicals (HO·) and sulfate radicals (SO4-·) were determined using a competition kinetics experiment, and the effects of persulfate concentration, pH, and inorganic anions on the degradation of CQP were also systematically studied. Furthermore, a kinetic model was established to predict the concentration of CQP and major free radicals to explore its mechanism of influence. The results showed that the degradation efficiency of CQP could reach 91.3% after 10 min under UV/PS, which was significantly higher than that under UV, sunlight, or PS alone. At pH=6.9, the second-order rate reaction constants of CQP with HO· and SO4-· were 8.9×109 L·(mol·s)-1and 1.4×1010 L·(mol·s)-1, respectively, and the main active species was SO4-·. The degradation rate of CQP increased with increasing concentrations of PS and decreased with the addition of HCO3- and Cl-. The removal efficiency of CQP was inhibited under stronger alkaline conditions. N-de-ethylation, cleavage of the C-N bond, and hydrogen abstraction were proposed as the principal pathways of CQP degradation based on LC-MS analysis. The mineralization rate of CQP could be improved by increasing PS concentration and pH values. This study could be helpful for the treatment of anti-COVID-19 pharmaceutical wastewater.

A multi-centre, randomized, double-blind, placebo-controlled clinical trial of the efficacy and safety of chloroquine phosphate, hydroxychloroquine sulphate and lopinavir/ritonavir for the treatment of COVID-19 in Lagos State: study protocol for a randomized controlled trial.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that was first identified in Wuhan, Hubei, China, in December 2019. It was recognized as a pandemic by the World Health Organization on 11 March 2020. Outbreak forecasting and mathematical modelling suggest that these numbers will continue to rise. Early identification of effective remedies that can shorten the duration and severity of illness is critical for Lagos State, which is the epi-centre of the disease in Nigeria. METHODS: This is a multi-centre, randomized, double-blind placebo-controlled superiority trial. The study investigates the efficacy of chloroquine phosphate, hydroxychloroquine sulphate and lopinavir/ritonavir added on to standard of care compared to standard of care only in patients with COVID-19 disease. The primary outcome is the clinical status of patients measured using a 7-point ordinal scale at day 15. Research participants and clinicians will be blinded to the allocated intervention. Outcome measures will be directly assessed by clinicians. Statistical analysis will be done by a team blinded to the identity and allocation of research participants. Data analysis will follow intention-to-treat methods, using R software. DISCUSSION: The current study is of strategic importance for Lagos State in potentially curbing the health, social and economic burden of COVID-19 disease. Should the current study demonstrate that either of the three intervention drugs is more efficacious than standard therapy alone, the State Ministry of Health will develop an evidence-based guideline for the management of COVID-19 in Lagos State. The findings will also be shared nationally and with other states which may lead to a standardized national guideline for the treatment of COVID-19 in Nigeria. TRIAL REGISTRATION: Pan African Clinical Trials Register PACTR202004801273802 . Registered prospectively on April 2, 2020.

Cationic Compounds with SARS-CoV-2 Antiviral Activity and Their Interaction with Organic Cation Transporter/Multidrug and Toxin Extruder Secretory Transporters.

In the wake of the COVID-19 pandemic, drug repurposing has been highlighted for rapid introduction of therapeutics. Proposed drugs with activity against SARS-CoV-2 include compounds with positive charges at physiologic pH, making them potential targets for the organic cation secretory transporters of kidney and liver, i.e., the basolateral organic cation transporters, OCT1 and OCT2; and the apical multidrug and toxin extruders, MATE1 and MATE2-K. We selected several compounds proposed to have in vitro activity against SARS-CoV-2 (chloroquine, hydroxychloroquine, quinacrine, tilorone, pyronaridine, cetylpyridinium, and miramistin) to test their interaction with OCT and MATE transporters. We used Bayesian machine learning models to generate predictions for each molecule with each transporter and also experimentally determined IC50 values for each compound against labeled substrate transport into CHO cells that stably expressed OCT2, MATE1, or MATE2-K using three structurally distinct substrates (atenolol, metformin and 1-methyl-4-phenylpyridinium) to assess the impact of substrate structure on inhibitory efficacy. For the OCTs substrate identity influenced IC50 values, although the effect was larger and more systematic for OCT2. In contrast, inhibition of MATE1-mediated transport was largely insensitive to substrate identity. Unlike MATE1, inhibition of MATE2-K was influenced, albeit modestly, by substrate identity. Maximum unbound plasma concentration/IC50 ratios were used to identify potential clinical DDI recommendations; all the compounds interacted with the OCT/MATE secretory pathway, most with sufficient avidity to represent potential DDI issues for secretion of cationic drugs. This should be considered when proposing cationic agents as repurposed antivirals. SIGNIFICANCE STATEMENT: Drugs proposed as potential COVID-19 therapeutics based on in vitro activity data against SARS-CoV-2 include compounds with positive charges at physiological pH, making them potential interactors with the OCT/MATE renal secretory pathway. We tested seven such molecules as inhibitors of OCT1/2 and MATE1/2-K. All the compounds blocked transport activity regardless of substrate used to monitor activity. Suggesting that plasma concentrations achieved by normal clinical application of the test agents could be expected to influence the pharmacokinetics of selected cationic drugs.

Effect of drug metabolism in the treatment of SARS-CoV-2 from an entirely computational perspective.

Understanding the effects of metabolism on the rational design of novel and more effective drugs is still a considerable challenge. To the best of our knowledge, there are no entirely computational strategies that make it possible to predict these effects. From this perspective, the development of such methodologies could contribute to significantly reduce the side effects of medicines, leading to the emergence of more effective and safer drugs. Thereby, in this study, our strategy is based on simulating the electron ionization mass spectrometry (EI-MS) fragmentation of the drug molecules and combined with molecular docking and ADMET models in two different situations. In the first model, the drug is docked without considering the possible metabolic effects. In the second model, each of the intermediates from the EI-MS results is docked, and metabolism occurs before the drug accesses the biological target. As a proof of concept, in this work, we investigate the main antiviral drugs used in clinical research to treat COVID-19. As a result, our strategy made it possible to assess the biological activity and toxicity of all potential by-products. We believed that our findings provide new chemical insights that can benefit the rational development of novel drugs in the future.

No difference in biomarkers of ischemic heart injury and heart failure in patients with COVID-19 who received treatment with chloroquine phosphate and those who did not.

BACKGROUND: Chloroquine was promoted as a COVID-19 therapeutic early in the pandemic. Most countries have since discontinued the use of chloroquine due to lack of evidence of any benefit and the risk of severe adverse events. The primary aim of this study was to examine if administering chloroquine during COVID-19 imposed an increased risk of ischemic heart injury or heart failure. METHODS: Medical records, laboratory findings, and electrocardiograms of patients with COVID-19 who were treated with 500 mg chloroquine phosphate daily and controls not treated with chloroquine were reviewed retrospectively. Controls were matched in age and severity of disease. RESULTS: We included 20 patients receiving chloroquine (500 mg twice daily) for an average of five days, and 40 controls. The groups were comparable regarding demographics and biochemical analyses including C-reactive protein, thrombocytes, and creatinine. There were no statistically significant differences in cardiac biomarkers or in electrocardiograms. Median troponin T was 10,8 ng/L in the study group and 17.9 ng/L in the control group, whereas median NT-proBNP was 399 ng/L in patients receiving chloroquine and 349 ng/L in the controls. CONCLUSIONS: We found no increased risk of ischemic heart injury or heart failure as a result of administering chloroquine. However, the use of chloroquine to treat COVID-19 outside of clinical trials is not recommended, considering the lack of evidence of its effectiveness, as well as the elevated risk of fatal arrythmias.

Risk factors for prolonged virus shedding of respiratory tract and fecal in adults with severe acute respiratory syndrome coronavirus-2 infection.

BACKGROUND: The dynamic alteration and comparative study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding pattern during treatment are limited. This study explores the potential risk factors influencing prolonged viral shedding in COVID-19. METHODS: A total of 126 COVID-19 patients were enrolled in this retrospective longitudinal study. A multivariate logistic regression analysis was carried out to estimate the potential risk factors. RESULTS: 38.1% (48/126) cases presented prolonged respiratory tract viral shedding, and 30 (23.8%) cases presented prolonged rectal swab viral shedding. Obesity (OR, 3.31; 95% CI, 1.08-10.09), positive rectal swab (OR, 3.43; 95% CI, 1.53-7.7), treatment by lopinavir/ritonavir with chloroquine phosphate (OR, 2.5; 95% CI, 1.04-6.03), the interval from onset to antiviral treatment more than 7 days (OR, 2.26; 95% CI, 1.04-4.93), lower CD4+ T cell (OR, 0.92; 95% CI, 0.86-0.99) and higher NK cells (OR, 1.11; 95% CI, 1.02-1.20) were significantly associated with prolonged respiratory tract viral shedding. CD3-CD56+ NK cells (OR, 0.87; 95% CI, 0.76-0.99) were related with prolonged fecal shedding. CONCLUSIONS: Obesity, delayed antiviral treatment, and positive SARS-CoV-2 for stool were independent risk factors for prolonged SARS-CoV-2 RNA shedding of the respiratory tract. A combination of LPV/r and abidol as the initial antiviral regimen was effective in shortening the duration of viral shedding compared with LPV/r combined with chloroquine phosphate. CD4+ T cell and NK cells were significantly associated with prolonged viral shedding, and further studies are to be warranted to determine the mechanism of immunomodulatory response in virus clearance.

Treatment strategies of hospitalized patients with coronavirus disease-19.

With the outbreak of coronavirus disease-19 (COVID-19), Changsha faced an increasing burden of treating the Wuhan migrants and their infected patients. This study is a retrospective, single-center case series of the 238 consecutive hospitalized patients with confirmed COVID-19 at the First Hospital of Changsha city, China, from 01/21 to 02/14, 2020; the final date of follow-up was 02/27, 2020. Of 238 patients 43.7% visited Wuhan, 58.4% got in touch with Wuhan people, and 47.5% had contacted with diagnosed patients. 37.8% patients had family members infected. 190 cases had mild / general disease, and 48 cases had severe / critical disease. Compared to mild or general patients, more severe or critical patients visited Wuhan (59.6% vs 40.2%; P=0.02) and contacted with Wuhan people (74.5% vs 55.0%; P=0.02). All patients received antiviral treatment, including Lopinavir / Ritonavir (29.3%), Interferon (14.6%) and their combination (40.6%), Arbidol (6.7%), Xuebijing (7.1%) and Chloroquine phosphate (1.3%). Severe and critical patients received glucocorticoid, Gamma-globulin and oxygen inhalation. Some received mechanic ventilation support. As of 02/27, 161 patients discharged. The median length of hospital stay was 13 days. The 10-, 14-, 20- and 28-day discharge rate was 19.1%, 42.8%, 65.0% and 76.4%, respectively. No hospital-related transmission was observed.

Development of an easy and rapid analytical method for the extraction and preconcentration of chloroquine phosphate from human biofluids prior to GC-MS analysis.

A vortex assisted spraying based fine droplet formation liquid phase microextraction (VA-SFDF-LPME) method was developed to determine chloroquine phosphate at trace levels in human serum, urine and saliva samples by gas chromatography-mass spectrometry (GC-MS) with single quadrupole mass analyzer. In the first part, several liquid phase microextraction (LPME) and magnetic solid phase extraction (MSPE) methods were compared to each other in order to observe their extraction ability for the analyte. VA-SFDF-LPME method was selected as an efficient and easy extraction method due to its higher extraction efficiency. Optimization studies were carried out for the parameters such as extraction solvent type, sodium hydroxide volume/concentration, sample volume, spraying number and mixing type/period. Tukey's method based on post hoc test was applied to all experimental data for the selection of optimum values. Optimum extraction parameters were found to be 12 mL initial sample volume, two sprays of dichloromethane, 0.75 mL of 60 g/kg sodium hydroxide and 15 s vortex. Under the optimum conditions, limit of detection and quantification (LOD and LOQ) were calculated as 2.8 and 9.2 µg/kg, respectively. Detection power of the GC-MS system was increased by approximately 317 folds with the developed extraction/preconcentration method. The applicability and accuracy of the proposed method was evaluated by spiking experiments and percent recovery results for human urine, serum and saliva samples were found in the range of 90.9% and 114.0% with low standard deviation values (1.9-9.4).

Development and validation of an LC-MS/MS method for determination of hydroxychloroquine, its two metabolites, and azithromycin in EDTA-treated human plasma.

BACKGROUND: Hydroxychloroquine (HCQ) and azithromycin (AZM) are antimalarial drugs recently reported to be active against severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2), which is causing the global COVID-19 pandemic. In an emergency response to the pandemic, we aimed to develop a quantitation method for HCQ, its metabolites desethylhydroxychloroquine (DHCQ) and bisdesethylchloroquine (BDCQ), and AZM in human plasma. METHODS: Liquid chromatography tandem mass spectrometry was used to develop the method. Samples (20 µL) are extracted by solid-phase extraction and injected onto the LC-MS/MS system equipped with a PFP column (2.0 × 50 mm, 3 µm). ESI+ and MRM are used for detection. Ion pairs m/z 336.1→247.1 for HCQ, 308.1→179.1 for DHCQ, 264.1→179.1 for BDCQ, and 749.6→591.6 for AZM are selected for quantification. The ion pairs m/z 342.1→253.1, 314.1→181.1, 270.1→181.1, and 754.6→596.6 are selected for the corresponding deuterated internal standards (IS) HCQ-d4, DHCQ-d4, BDCQ-d4, and AZM-d5. The less abundant IS ions from 37Cl were used to overcome the interference from the analytes. RESULTS: Under optimized conditions, retention times are 0.78 min for BDCQ, 0.79 min for DHCQ, 0.92 min for HCQ and 1.87 min for AZM. Total run time is 3.5 min per sample. The calibration ranges are 2-1000 ng/mL for HCQ and AZM, 1-500 ng/mL for DHCQ and 0.5-250 ng/mL for BDCQ; samples above the range are validated for up to 10-fold dilution. Recoveries of the method ranged from 88.9-94.4% for HCQ, 88.6-92.9% for DHCQ, 88.7-90.9% for BDCQ, and 98.6%-102% for AZM. The IS normalized matrix effect were within (100±10) % for all 4 analytes. Blood samples are stable for at least 6 hr at room temperature. Plasma samples are stable for at least 66 hr at room temperature, 38 days at -70°C, and 4 freeze-thaw cycles. CONCLUSIONS: An LC-MS/MS method for simultaneous quantitation of HCQ, DHCQ, BDCQ, and AZM in human plasma was developed and validated for clinical studies requiring fast turnaround time and small samples volume.

Determining available strategies for prevention and therapy: Exploring COVID­19 from the perspective of ACE2 (Review).

Coronavirus disease 2019 (COVID­19) is an acute infectious pneumonia caused by a novel type of coronavirus infection. There are currently no clinically available specific drugs for the treatment of this virus. The process of host invasion is the key to viral infection, and it is a mechanism that needs to be considered when exploring antiviral drugs. At present, studies have confirmed that angiotensin­converting enzyme II (ACE2) is the main functional receptor through which severe acute respiratory syndrome coronavirus (SARS­CoV­2) invades host cells. Therefore, a number of studies have focused on this field. However, as ACE2 may play a dual role in mediating susceptibility and immunity to SARS­CoV­2 infection, the role of ACE2 in viral infection is controversial. Beginning with the physiological function of ACE2, the present review article summarizes the influence of the ACE2 content on the susceptibility to the virus and acute lung injury. Drug mechanisms were taken as the starting point, combined with the results of clinical trials, specifically elaborating upon and analyzing the efficacy of several ACE2­centered therapeutic drugs and their potential effects. In addition, the current status of ACE2 as a targeted therapy for COVID­19 is discussed in order to provide new insight into the clinical prevention and treatment of COVID­19.

Clinical characteristics of COVID-19 patients hospitalized at Clinique Ngaliema, a public hospital in Kinshasa, in the Democratic Republic of Congo: A retrospective cohort study.

OBJECTIVES: To describe the clinical characteristics of patients infected with SARS-CoV-2 at Clinique Ngaliema, a public hospital, in Kinshasa, in the Democratic Republic of Congo (DRC). METHODS: This retrospective study analyzed medical records including socio-demographics, past medical history, clinical manifestation, comorbidities, laboratory data, treatment and disease outcome of 160 hospitalized COVID-19 patients, with confirmed result of SARS-CoV-2 viral infection. RESULTS: The median age of patients was 54 years (IQR: 38-64), and there was no significant gender difference (51% of male). The most common comorbidities were hypertension (55 [34%]), diabetes (31 [19%]) and obesity (13 [8%]). Fever (93 [58%]), cough (92 [57%]), fatigue (87 [54%]), shortness of breath (72 [45%]) and myalgia (33 [21%]) were the most common symptoms, upon admission. Patients were categorized into mild (92 [57%]), moderate (19 [12%]) and severe (49 [31%]). Severe patients were older and were more likely to have comorbidities, compared to mild ones. The majority of patients (92% [147 of 160]) patients received hydroxychloroquine or chloroquine phosphate. Regression model revealed that older age, lower SpO2, higher heart rate and elevated AST at admission were all risk factors associated with in-hospital death. The prevalence of COVID-19 and malaria co-infection was 0.63% and 70 (44%) of all patients received antimalarial treatment before hospitalization. CONCLUSION: Our findings indicated that the epidemiological and clinical feature of COVID-19 patients in Kinshasa are broadly similar to previous reports from other settings. Older age, lower SpO2, tachycardia, and elevated AST could help to identify patients at higher risk of death at an early stage of the illness. Plasmodium spp co-infection was not common in hospitalized COVID-19 patients.

Cracking the Chloroquine Conundrum: The Application of Defective UiO-66 Metal-Organic Framework Materials to Prevent the Onset of Heart Defects-In Vivo and In Vitro.

In this study, we present a modulated synthesis nanocrystalline defective UiO-66 metal-organic framework as a potential chloroquine diphosphate (CQ) delivery system. Increasing the concentration of hydrochloric acid during the modulated synthesis resulted in a considerable increase of pore volume, which enhanced the CQ loading in CQ@UiO-66 composites. Drug release tests for CQ@UiO-66 composites have confirmed prolonged CQ release in comparison with pure CQ. In vivo tests on a Danio reiro model organism have revealed that CQ released from CQ@UiO-66 25% showed lower toxicity and fewer cardiotoxic effects manifested by cardiac malformations and arrhythmia in comparison to analogous doses of CQ. Cytotoxicity tests proved that the CQ loaded on the defective UiO-66 cargo resulted in increased viability of cardiac cells (H9C2) as compared to incubation with pure CQ. The experimental results presented here may be a step forward in the context of reducing the cardiotoxicity CQ.

Lack of protective effect of chloroquine derivatives on COVID-19 disease in a Spanish sample of chronically treated patients.

BACKGROUND: The search for a SARS-CoV-2 treatment has emerged as a worldwide priority. We evaluated the role of chloroquine and its derivatives in COVID-19 in Spanish individuals. METHODS: We performed a survey addressed to patients regularly taking chloroquine and its derivatives for the control of their autoimmune diseases. The survey was distributed with special attention to Spanish patient associations centred on autoimmune diseases and rheumatology and to the general population. A sample of untreated subjects was matched to the treated group according to sex, age range and incidence region. COVID-19 disease prevalence was compared between treated and untreated-matched control sample. RESULTS: A total of 319 surveys of patients regularly taking chloroquine and its derivatives were recovered for further analysis. The prevalence of declared COVID-19 status in the treated group was 5.3% and the mean prevalence among the untreated-matched groups was 3.4%. A community exposition to COVID-19 was associated with a greater prevalence of COVID-19 in both, treated (17.0% vs. 3.2%; p-value<0.001) and untreated groups (13.4% vs. 1.1%; p-value = 0.027). CONCLUSION: We did not find differences of reported COVID-19 cases between treated and untreated groups, indicating a lack of protection by regular administration of chloroquine and its derivative drugs on COVID-19 infection. Of relevance, data indicates that patients that regularly take chloroquine derivatives are exposed to SARS-CoV-2 infection and must take the same protection measures as the general population.

Theoretical Insights into the Anti-SARS-CoV-2 Activity of Chloroquine and Its Analogs and In Silico Screening of Main Protease Inhibitors.

Corona virus disease (COVID-19) is a dangerous disease rapidly spreading all over the world today. Currently there are no treatment options for it. Drug repurposing studies explored the potency of antimalarial drugs, chloroquine and hydroxychloroquine, against SARS-CoV-2 virus. These drugs can inhibit the viral protease, called chymotrypsin-like cysteine protease, also known as Main protease (3CLpro); hence, we studied the binding efficiencies of 4-aminoquinoline and 8-aminoquinoline analogs of chloroquine. Six compounds furnished better binding energies than chloroquine and hydroxychloroquine. The interactions with the active site residues especially with Cys145 and His41, which are involved in catalytic diad for proteolysis, make these compounds potent main protease inhibitors. A regression model correlating binding energy and the molecular descriptors for chloroquine analogs was generated with R2 = 0.9039 and Q2 = 0.8848. This model was used to screen new analogs of primaquine and molecules from the Asinex compound library. The docking and regression analysis showed these analogs to be more potent inhibitors of 3CLpro than hydroxychloroquine and primaquine. The molecular dynamic simulations of the hits were carried out to determine the binding stabilities. Finally, we propose four compounds that show drug likeness toward SARS-CoV-2 that can be further validated through in vitro and in vivo studies.

Population-based meta-analysis of chloroquine: informing chloroquine pharmacokinetics in COVID-19 patients.

AIMS: Chloroquine (CQ) has been repurposed to treat coronavirus disease 2019 (COVID-19). Understanding the pharmacokinetics (PK) in COVID-19 patients is essential to study its exposure-efficacy/safety relationship and provide a basis for a possible dosing regimen optimization. SUBJECT AND METHODS: In this study, we used a population-based meta-analysis approach to develop a population PK model to characterize the CQ PK in COVID-19 patients. An open-label, single-center study (ethical review approval number: PJ-NBEY-KY-2020-063-01) was conducted to assess the safety, efficacy, and pharmacokinetics of CQ in patients with COVID-19. The sparse PK data from 50 COVID-19 patients, receiving 500 mg CQ phosphate twice daily for 7 days, were combined with additional CQ PK data from 18 publications. RESULTS: A two-compartment model with first-order oral absorption and first-order elimination and an absorption lag best described the data. Absorption rate (ka) was estimated to be 0.559 h-1, and a lag time of absorption (ALAG) was estimated to be 0.149 h. Apparent clearance (CL/F) and apparent central volume of distribution (V2/F) was 33.3 l/h and 3630 l. Apparent distribution clearance (Q/F) and volume of distribution of peripheral compartment (Q3/F) were 58.7 l/h and 5120 l. The simulated CQ concentration under five dosing regimens of CQ phosphate were within the safety margin (400 ng/ml). CONCLUSION: Model-based simulation using PK parameters from the COVID-19 patients shows that the concentrations under the currently recommended dosing regimen are below the safety margin for side-effects, which suggests that these dosing regimens are generally safe. The derived population PK model should allow for the assessment of pharmacokinetics-pharmacodynamics (PK-PD) relationships for CQ when given alone or in combination with other agents to treat COVID-19.

Composition analysis of falsified chloroquine phosphate samples seized during the COVID-19 pandemic.

The proliferation of falsified medicines can cause serious public health issues, particularly in the context of a global pandemic such as the actual COVID-19 pandemic. Our study involved eight chloroquine phosphate medicines seized in Cameroon, Democratic Republic of Congo and Niger during March and May 2020. These suspect samples were first analyzed in a screening phase using field tools such as handheld Raman spectroscopy (TruScan) and then in a confirmation phase using laboratory tools such as hyperspectral Raman imaging and High Performance Liquid Chromatography (HPLC). The results confirmed the falsified nature of the samples, highlighting the presence of metronidazole at low dose in four samples (16.6, 15.2, 15.2 and 14.5 mg/tab), too low levels of chloroquine in two samples (2.4 and 20.2 mg/tab), and substitution of chloroquine phosphate by paracetamol in one sample (255.7 mg/tab). The results also confirmed that four samples had been adulterated with paracetamol in trace amounts and two of them presented traces of chloramphenicol.

Pharmacological and cardiovascular perspectives on the treatment of COVID-19 with chloroquine derivatives.

The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and an ongoing severe pandemic. Curative drugs specific for COVID-19 are currently lacking. Chloroquine phosphate and its derivative hydroxychloroquine, which have been used in the treatment and prevention of malaria and autoimmune diseases for decades, were found to inhibit SARS-CoV-2 infection with high potency in vitro and have shown clinical and virologic benefits in COVID-19 patients. Therefore, chloroquine phosphate was first used in the treatment of COVID-19 in China. Later, under a limited emergency-use authorization from the FDA, hydroxychloroquine in combination with azithromycin was used to treat COVID-19 patients in the USA, although the mechanisms of the anti-COVID-19 effects remain unclear. Preliminary outcomes from clinical trials in several countries have generated controversial results. The desperation to control the pandemic overrode the concerns regarding the serious adverse effects of chloroquine derivatives and combination drugs, including lethal arrhythmias and cardiomyopathy. The risks of these treatments have become more complex as a result of findings that COVID-19 is actually a multisystem disease. While respiratory symptoms are the major clinical manifestations, cardiovascular abnormalities, including arrhythmias, myocarditis, heart failure, and ischemic stroke, have been reported in a significant number of COVID-19 patients. Patients with preexisting cardiovascular conditions (hypertension, arrhythmias, etc.) are at increased risk of severe COVID-19 and death. From pharmacological and cardiovascular perspectives, therefore, the treatment of COVID-19 with chloroquine and its derivatives should be systematically evaluated, and patients should be routinely monitored for cardiovascular conditions to prevent lethal adverse events.

A contemporary look at COVID-19 medications: available and potentially effective drugs.

OBJECTIVE: There have been significant changes to the management of COVID-19 in recent months, including protocols and guidelines designed to prevent, diagnose, and treat the Novel Coronavirus (COVID-19). Several management options have been suggested and have since gained popularity, though we expect additional modifications to be made, as well as more new cases in the coming months, given a lack of definitive treatment and well-controlled experiments. This review highlights the available and potential treatments, along with the challenges associated with each. MATERIALS AND METHODS: We conducted a comprehensive overview of all peer-reviewed studies, editorial comments, and letters to the editor based on a search in PubMed, Google Scholar, Web of Science, and Scopus. The following terms were used: "COVID-19," "SARS-CoV-2," "drug," "treatment," "medication," and "management." All searches were done between March and May 20, 2020. RESULTS: There are several potential medications available for COVID-19, such as Interferon α (IFN-α), Teicoplanin, Ribavirin, Galidesivir, Lopinavir/Ritonavir, Chloroquine phosphate, Arbidol, Velpatasvir, Favipiravir, Ledipasvir, Remdesivir, Sofosbuvir, Darunavir, Qingfei Paidu Decoction (QPD), and Imatinib. However, we do not have a definitive and specific treatment yet. CONCLUSIONS: We are expecting to have more cases in the coming weeks/months. Therefore, further research is needed to characterize the disease behavior, to find the absolute drug, and to refine the treatment.