Self-medication among university students during the COVID-19 pandemic: a comparative analysis of different faculties

Self-medication is a widespread public health concern. University students are likely to be more prone to it since self-medication rates increase with educational level. Studies have shown that self-medication rates vary among academics belonging to different faculties, and medical students have the highest self-medication rates. However, it is unknown whether this holds in a vulnerable situation, such as the COVID-19 pandemic. It is also unknown whether differences in technical knowledge of drugs influence self-medication rates among students. Thus, this study analyzes and compares prophylactic self-medication among graduate students of different faculties in the context of the COVID-19 pandemic. This cross-sectional observational study was conducted at a private university in southern Brazil. Students from the medicine, law, life sciences, and fine arts faculties were surveyed, and their responses were compared using a chi-square test. Among 396 respondents, 29.5% reported using preventive medication for COVID-19, and medical students were the least likely to do so. The self-medication rate was 13.6% among respondents, and self-medication did not differ significantly between students of different faculties. Of the students who self-medicated 63% reported having studied the medication before using them. Furthermore, the media did not induce drug use among 81.8% respondents. These results show that medical students used fewer preventive medications during the pandemic and refute the assertion that self-medication rates are higher among medical students. They also show that self-medication rates during the pandemic were significantly lower than those before the pandemic. These revelations show a new aspect of self-medication.Copyright © 2021 Muslim OT et al.

Nitazoxanide and azithromycin for the early treatment of COVID-19: A multi-spectroscopic, biochemical and computational drug–drug interaction study

Herein, we present an experimental and theoretical drug–drug interaction study between nitazoxanide (NTZ) and azithromycin (AZT) in an aqueous solution. Interaction was studied by using UV/Vis, fluorescence, attenuated total reflectance-fourier transform infrared (ATR-FTIR), and circular dichroism (CD) spectroscopy, while molecular docking studies were performed to establish the interaction computationally. A bright yellow color was observed when the two drugs interacted, giving a hyperchromic band at 420 nm. The rate of absorbance was linearly increased by increasing drug concentrations and in a time-dependent manner. Stability of the interaction complex (i.e., NTZ: AZT) was measured at variable temperatures (25–80°C), pH (5.0–10.0) and ionic strength (0.05–2.0 M NaCl), and not only proved stable but also retained antimicrobial potential with reduced cellular toxicity. Mole ratio and Job's method of continuous variations were used to establish the binding stoichiometry and found to be 2:1. The calculated binding constant (kb = 8,400 M−1) and Gibb's free energy (ΔG° = −22.4 KJ/mol) also suggested an energetically favorable interaction. FTIR spectra of NTZ: AZT complex in comparison with two drugs alone revealed significant interaction which was nicely complemented by molecular docking studies. Interaction was also successfully demonstrated in presence of carrier protein HSA and by spiking the two drugs in real samples of human plasma and urine. © 2023 The Chemical Society Located in Taipei & Wiley-VCH GmbH.

Mechanism and Kinetics of The Degradation of Nitazoxanide and Hydroxychloroquine Drugs by Hydroxyl Radicals: Theoretical Approach to Ecotoxicity

The efforts of contrasting the effects caused by the Covid-19 (coronavirus disease 2019) pandemic increased the disposal of active pharmaceutical ingredients. This paper reports the mechanisms and kinetics of the degradation in aqueous environments induced by 'OH of two drugs, among those most widely probed at the outbreak of coronavirus, nitazoxanide and hydroxychloroquine. The investigation exploits quantum chemistry techniques and a reaction rate theory combined with diffusion-controlled processes and quantum mechanical tunneling. The reaction rate constants are obtained in an environmentally relevant temperature range. The results show that (i) the deacetylation of nitazoxanide with formation of tizoxanide is kinetically the most favorable channel, in agreement with experimental work;(ii) for hydroxychloroquine, the present theoretical calculations show that the most favorable channel is the addition of 'OH at the aromatic ring. The half-life time degradation products are for both cases in the range between 12 to 138 days. Both drugs presented toxicities between harmful and toxic as obtained by computational toxicology calculations: The toxicity is also calculated for the degradation products: (i) in the nitazoxanide degradation process, tizoxanide was characterized as more toxic, while (ii) in the case of hydroxychloroquine, the major degradation product showed a decrease in the toxicity.

Off Label Medication to Combat COVID-19: Review Results to Date

Background: Severe viral pneumonia cases were observed in the people of Wuhan, China in December 2019. It has already affected almost every country around the globe and was declared a pandemic by the World Health Organization. We aim to evaluate the therapeutics and safety of various off label COVID-19 drugs. Method(s): PubMed, Research Gate, Science Direct, Google Scholar, Centre for Disease control and prevention (CDC) portal, Chinese Centre for Disease Control and prevention (CCDC) portal, World Health Organization (WHO) portal were searched for obtaining reliable data. Result(s): COVID-19 is creating a storm of deaths and active cases globally, which is forcing the pharmaceutical companies and scientists to work day and night to find an effective and safer anti-COVID-19 medication. Various in vitro and clinical trials had been performed as well as are currently ongoing to analyze the mechanisms and therapeutics of off label medications like Chloroquine, Hydroxychloro-quine, Amodiaquine, Azithromycin, Remdesivir, Favipiravir, Ritonavir/Lopinavir, Umifenovir, Osel-tamivir, Ribavirin, Nafamostat, Camostat, Tocilizumab, Ivermectin, Nitazoxanide, Famotidine, Vitamin D, Corticosteroids and Dexamethasone. In vitro studies were performed by utilizing Vero E6 cells and hSLAM cells while open/closed, randomized/non-randomized, single-centered/multi-centered and retrospective clinical trials and case studies were organized to determine their safety and efficacy. Conclusion(s): Although these drugs have shown promising results against COVID-19 patients, it cannot be concluded that these drugs are truly safe and effective because there are no conclusive evidence to support the facts since only limited researches and studies had been investigated.Copyright © 2021 Bentham Science Publishers.

Major Drugs Used in COVID-19 Treatment: Molecular Mechanisms, Vali-dation and Current Progress in Trials

Background: Currently, the present world is facing a new deadly challenge from a pandemic disease called COVID-19, which is caused by a coronavirus named SARS-CoV-2. To date, no drug or vaccine can treat COVID-19 completely, but some drugs have been used primarily, and they are in different stages of clinical trials. This review article discussed and compared those drugs which are running ahead in COVID-19 treatments. Method(s): We have explored PUBMED, SCOPUS, WEB OF SCIENCE, as well as press releases of WHO, NIH and FDA for articles related to COVID-19 and reviewed them. Result(s): Drugs like favipiravir, remdesivir, lopinavir/ritonavir, hydroxychloroquine, azithromycin, ivermectin, corticosteroids and interferons have been found effective to some extent, and partially approved by FDA and WHO to treat COVID-19 at different levels. However, some of these drugs have been disapproved later, although clinical trials are going on. In parallel, plasma therapy has been found fruitful to some extent too, and a number of vaccine trials are going on. Conclusion(s): This review article discussed the epidemiologic and mechanistic characteristics of SARS-CoV-2, and how drugs could act on this virus with the comparative discussion on progress and drawbacks of major drugs used till date, which might be beneficial for choosing therapies against COVID-19 in different countries.Copyright © 2022 Bentham Science Publishers.

COVID-19: From the Molecular Mechanisms to Treatment

The 2019 novel coronavirus (SARS-CoV-2) causes severe pneumonia called COVID-19 and leads to severe acute respiratory syndrome with a high mortality rate. The SARS-CoV-2 virus in the human body leads to jumpstarting immune reactions and multi-organ inflammation, which has poorer outcomes in the presence of predisposing conditions, including hypertension, dyslipidemia, dysglycemia, abnormal adiposity, and even endothelial dysfunction via biomolecular mechanisms. In addition, leucopenia, hypoxemia, and high levels of both cytokines and chemokines in the acute phase of this disease, as well as some abnormalities in chest CT images, were reported in most patients. The spike protein in SARS-CoV-2, the primary cell surface protein, helps the virus anchor and enter the human host cells. Additionally, new mutations have mainly happened for spike protein, which has promoted the infection's transmissibility and severity, which may influence manufactured vaccines' efficacy. The exact mechanisms of the pathogenesis, besides molecular aspects of COVID-19 related to the disease stages, are not well known. The altered molecular functions in the case of immune responses, including T CD4+, CD8+, and NK cells, besides the overactivity in other components and outstanding factors in cytokines like interleukin-2, were involved in severe cases of SARS-CoV-2. Accordingly, it is highly needed to identify the SARS-CoV-2 bio-molecular characteristics to help identify the pathogenesis of COVID-19. This study aimed to investigate the bio-molecular aspects of SARS-CoV-2 infection, focusing on novel SARS-CoV-2 variants and their effects on vaccine efficacy.Copyright © 2022 NRITLD, National Research Institute of Tuberculosis and Lung Disease, Iran.

The Outbreak of Coronavirus Disease 2019 (COVID-19) and its Manifestation

The outbreak of coronavirus disease 2019 (COVID-19) was first reported in Wuhan, Chi-na, and soon the infection turned into a pandemic. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the spread of COVID-19 infection. The World Health Organization (WHO) confirmed 4.20% of total deaths globally (March 21, 2020). Within four months (July 21, 2020), the rate of confirmed total deaths was recorded up to 4.17% globally. In India, 909 confirmed cases and 19 deaths were reported by Health and Family Welfare, Government of India, on March 28, 2020. Over a period of 123 days in India, 1638870 confirmed cases and 35684 deaths were reported. COVID-19 can potentially spread from person to person through direct contact or respiratory droplets from coughing and sneezing. The most common symptoms are fever, dry cough, difficulty in breathing, and fatigue. A pregnant mother with COVID-19 has fewer chances of trans-ferring this infection to her newborn baby. Children are less affected than adults from this virus. A specific antiviral drug or vaccine has not been developed to cure the disease to date. Drugs including chloroquine, hydroxychloroquine, lopinavir, ritonavir, nafamostat, nitazoxanide, and remde-sivir, have been observed to be effective for treating COVID-19. Many vaccine candidates are under investigation in pre-clinical and clinical studies. In this review, we highlight the epidemiology, signs and symptoms, pathogenesis, and mode of transmission of the infection caused by COVID-19, and its effects on a pregnant mother and newborn, and children. We also highlight the preventive measures and drugs that are effective for treating COVID-19.Copyright © 2021 Bentham Science Publishers.

Therapeutic potential of salicylamide derivatives for combating viral infections.

Since time immemorial human beings have constantly been fighting against viral infections. The ongoing and devastating coronavirus disease 2019 pandemic represents one of the most severe and most significant public health emergencies in human history, highlighting an urgent need to develop broad-spectrum antiviral agents. Salicylamide (2-hydroxybenzamide) derivatives, represented by niclosamide and nitazoxanide, inhibit the replication of a broad range of RNA and DNA viruses such as flavivirus, influenza A virus, and coronavirus. Moreover, nitazoxanide was effective in clinical trials against different viral infections including diarrhea caused by rotavirus and norovirus, uncomplicated influenza A and B, hepatitis B, and hepatitis C. In this review, we summarize the broad antiviral activities of salicylamide derivatives, the clinical progress, and the potential targets or mechanisms against different viral infections and highlight their therapeutic potential in combating the circulating and emerging viral infections in the future.

Real-world practice of the Egyptian Kelleni's protocol amid changing tropism of SARS-CoV-2 omicron BA.5.2.1.7, XBB 1.5 and CH.1.1 subvariants: a multi-purpose protocol.

The Egyptian immune-modulatory Kelleni's protocol, including nitazoxanide as an integral component, is being safely and effectively practiced to manage SARS-CoV-2, RSV, influenza infections in pediatric, adult and pregnant patients with negligible requirements for the relatively expensive diagnostic molecular tests. Most recently, Kelleni's protocol is being likewise used to manage potential norovirus infection which is currently confused with SARS-CoV-2 Omicron new enterotropic subvariants and the antihistaminic loratadine has been co-administered in selected patients. Notably, Africa has the least mandates, restrictions and SARS-CoV-2 vaccination rates and yet the least COVID-19 mortality.

Outpatient treatment of COVID-19: an experience with 552 cases in Mexico.

INTRODUCTION: The impact of the coronavirus disease 2019 (COVID-19) pandemic has globally challenged health services, especially because when the pandemic first reached Mexico, in February 2020, there was no known effective and safe treatment. A treatment scheme was offered by the Institute for the Integral Development of Health (IDISA) in Mexico City from March 2020 to August 2021 when there were many patients with COVID-19. This report summarizes the experience managing COVID-19 with this scheme. MATERIALS AND METHODS: This is a descriptive, retrolective study. The data was obtained from the case files of the patients who attended the IDISA from March 2020 to August 2021 with COVID-19. All the cases were treated with the scheme consisting of nitazoxanide, azithromycin, and prednisone. Various laboratory blood tests and chest computerized tomography scan were done. When indicated, supplementary oxygen, and another specific treatment were used. A standardized clinical recording was conducted for 20 days based on symptoms and systemic symptoms. RESULTS: Based on the World Health Organization criteria, the patients were classified according to the disease severity: 170 mild, 70 moderate, and 312 severe cases. The outcome was the discharge of 533 patients after their recovery, 16 were excluded from the study, and 6 died. CONCLUSIONS: The use of nitazoxanide, azithromycin, and prednisone proved to be effective as it resulted in improvement of symptoms and in successful outcomes for the management of COVID-19 outpatients.

Fast one-pot microwave-assisted green synthesis of highly fluorescent plant-inspired S,N-self-doped carbon quantum dots as a sensitive probe for the antiviral drug nitazoxanide and hemoglobin

In this study, we report a one-pot, green, cost-efficient, and fast synthesis of plant-based sulfur and nitrogen self-co-doped carbon quantum dots (S,N-CQDs). By 4-min microwave treatment of onion and cabbage juices as renewable, cheap, and green carbon sources and self-passivation agents, blue emissive S,N-CQDs have been synthesized (λex/λem of 340/418 nm) with a fluorescence quantum yield of 15.2%. A full characterization of the natural biomass-derived quantum dots proved the self-doping with nitrogen and sulfur. The S,N-CQDs showed high efficiency as a fluorescence probe for sensitive determination of nitazoxanide (NTZ), that recently found wide applicability as a repurposed drug for COVID-19, over the concentration range of 0.25–50.0 μM with LOD of 0.07 μM. The nanoprobe has been successfully applied for NTZ determination in pharmaceutical samples with excellent % recovery of 98.14 ± 0.42. Furthermore, the S,N-CQDs proved excellent performance as a sensitive fluorescence nanoprobe for determination of hemoglobin (Hb) over the concentration range of 36.3–907.5 nM with a minimum detectability of 10.30 nM. The probe has been applied for the determination of Hb in blood samples showing excellent agreement with the results documented by a medical laboratory. The greenness of the developed probe has been positively investigated by different greenness metrics and software. The green character of the proposed analytical methods originates from the synthesis of S,N-CQDs from sustainable, widely available, and cheap plants via low energy/low cost microwave-assisted technique. Omission of organic solvents and harsh chemicals beside dependence on mix-and-read analytical approach corroborate the method greenness. The obtained results demonstrated the substantial potential of the synthesized green, safe, cheap, and sustainable S,N-CQDs for pharmaceutical and biological applications. © 2022 Elsevier B.V.

Drug repurposing against SARS-CoV-2: A review based on principal reports

Despite the measures taken and the molecular advances for the development of new agents for the control of SARS-CoV-2 infection, there is still insufficient development of an effective treatment. The objective of the review was to de-scribe the clinical studies and reported articles on drugs used as possible therapeutic agents for COVID-19 and the main conclusions on their reuse. A non-systematic review through PubMed, ScienceDirect, and clinical trials at ClinicalTrials. gov on original articles and case report in English and Span-ish that will report information on COVID-19 treatment and its main conclusions. Articles that were not relevant or that did not mention updated information to that reported in other articles were excluded. A total of 99 bibliographic references were included. COVID-19 appears as a multisystemic disease with variable clinical symptoms. Since no specific treatment is yet known, multiple drugs have been proposed that attack the different pathways of SARS-CoV-2. For severe disease in patients who require hospitalization and oxygen support, the use of remdesivir, dexamethasone, or tocilizumab is recommended if there are patient conditions that apply to use them. The use of ivermectin, colchicine, lopinavir/ritonavir, hydroxy-chloroquine, and chloroquine have not reported benefits that surpass adverse effects.

Synthesis of active-site rich molybdenum-doped manganese tungstate nanocubes for effective electrochemical sensing of the antiviral drug (COVID-19) nitazoxanide.

Nitazoxanide (NTZ), a promising antiviral agent, is currently being tested in clinical trials as a potential treatment for novel coronavirus disease 2019 (COVID -19). This paper describes a one-pot hydrothermal synthesis to prepare molybdenum (Mo)-doped manganese tungstate nanocubes (Mo-MnWO4 NCs) for the electrochemical sensing of NTZ. The as-prepared Mo-MnWO4 NCs were characterized using various techniques such as XRD, Raman, FE-SEM, FE-TEM, and XPS to confirm the crystal structure, morphology, and elemental composition. The obtained results demonstrate that Mo doping on MnWO4 generates many vacancy sites, exhibiting remarkable electrochemical activity. The kinetic parameters of the electrode modified with Mo-MnWO4 NCs were calculated to be (Ks) 1.1 × 10-2 cm2 s-1 and (α) 0.97, respectively. Moreover, a novel electrochemical sensor using Mo-MnWO4 NCs was fabricated to detect NTZ, which is used as a primary antibiotic to control COVID-19. Under optimal conditions, the electrochemical reduction of NTZ was determined with a low detection limit of 3.7 nM for a linear range of 0.014-170.2 µM with a high sensitivity of 0.78 µA µM-1 cm-2 and negligible interference with other nitro group-containing drugs, cations, and anions. The electrochemical sensor was successfully used to detect NTZ in the blood serum and urine samples and achieved high recoveries in the range of 94-99.2% and 95.3-99.6%, respectively. This work opens a way to develop high-performance sensing materials by exploring the introduction of defect engineering on metal tungstates to detect drug molecules for practical applications.

A randomized, open-label trial of combined nitazoxanide and atazanavir/ritonavir for mild to moderate COVID-19.

Background: The nitazoxanide plus atazanavir/ritonavir for COVID-19 (NACOVID) trial investigated the efficacy and safety of repurposed nitazoxanide combined with atazanavir/ritonavir for COVID-19. Methods: This is a pilot, randomized, open-label multicenter trial conducted in Nigeria. Mild to moderate COVID-19 patients were randomly assigned to receive standard of care (SoC) or SoC plus a 14-day course of nitazoxanide (1,000 mg b.i.d.) and atazanavir/ritonavir (300/100 mg od) and followed through day 28. Study endpoints included time to clinical improvement, SARS-CoV-2 viral load change, and time to complete symptom resolution. Safety and pharmacokinetics were also evaluated (ClinicalTrials.gov ID: NCT04459286). Results: There was no difference in time to clinical improvement between the SoC (n = 26) and SoC plus intervention arms (n = 31; Cox proportional hazards regression analysis adjusted hazard ratio, aHR = 0.898, 95% CI: 0.492-1.638, p = 0.725). No difference was observed in the pattern of saliva SARS-CoV-2 viral load changes from days 2-28 in the 35% of patients with detectable virus at baseline (20/57) (aHR = 0.948, 95% CI: 0.341-2.636, p = 0.919). There was no significant difference in time to complete symptom resolution (aHR = 0.535, 95% CI: 0.251-1.140, p = 0.105). Atazanavir/ritonavir increased tizoxanide plasma exposure by 68% and median trough plasma concentration was 1,546 ng/ml (95% CI: 797-2,557), above its putative EC90 in 54% of patients. Tizoxanide was undetectable in saliva. Conclusion: Nitazoxanide co-administered with atazanavir/ritonavir was safe but not better than standard of care in treating COVID-19. These findings should be interpreted in the context of incomplete enrollment (64%) and the limited number of patients with detectable SARS-CoV-2 in saliva at baseline in this trial. Clinical trial registration: [https://clinicaltrials.gov/ct2/show/NCT04459286], identifier [NCT04459286].

Biological efficacy of novel metal complexes of Nitazoxanide: Synthesis, characterization, anti-COVID-19, antioxidant, antibacterial and anticancer activity studies.

It has been repeatedly reported that nitazoxanide (NTZ) exhibits a wide range of antiviral activities against various viral infections and has shown antimicrobial properties against anaerobic bacteria, helminths and protozoa. To improve these properties, three novel metal complexes were synthesized. The bidentate characteristic of the NTZ ligand was characterized by different spectroscopic techniques, including Fourier transform infrared (FT-IR), thermogravimetric, nuclear magnetic resonance (NMR) and UV - visible spectroscopy. The geometries of the formed compounds were evaluated by density functional theory, and the results revealed that NTZ-Ru(III) has an octahedral geometry, while NTZ-Au(III) and NTZ-Ag(I) complexes have distorted square planar structures. Binding between the metal complexes and calf thymus DNA (Ct-DNA) has been studied via absorption spectra. Moreover, human albumen serum (HAS) titration has been carried out to test their susceptibility to interact with a major target molecule via absorption and fluorescence spectroscopic techniques. Several in vitro bioassays were performed to evaluate the biological activity, antibacterial potency against E. coli, antioxidant activity and cytotoxicity of the ligand and the obtained complexes. The results showed that complexes Ru(III) and Au(III) have the highest radical scavenging percentage while the Ag(I) demonstrated the greatest antibacterial activity. Moreover, the metal complexes presented potentially effective against E. coli. Furthermore, compared with NTZ-Ag and the free ligand, the in vitro cytotoxicity assay showed that both NTZ-Ru(III) and NTZ-Au(III) exhibited significant anticancer activity against HeLa cells. The efficiency of the novel compounds as antivirals was tested by molecular docking with two COVID-19 receptors to obtain all interaction details.

Clinical outcomes, virological efficacy and safety of nitazoxanide in the treatment of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This study investigated the clinical outcomes, virological efficacy and safety of nitazoxanide in the treatment of patients with COVID-19. RESEARCH DESIGN AND METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for relevant articles written before August 23, 2022. Only randomized controlled trials (RCTs) that assessed the usefulness and safety of nitazoxanide in patients with COVID-19 were included. RESULTS: Five RCTs were included. The overall mortality of COVID-19 patients receiving nitazoxanide (study group) was 1.3% (9/670), which was lower than the control group (1.8%, 12/681), but this difference did not reach statistical significance (risk difference [RD], 0.00; 95% CI: -0.01 to 0.01; P =0.97). However, nitazoxanide was associated with a higher virological eradication rate than placebo or standard care (RD, 0.09; 95% CI: 0.01 to 0.17; P = 0.03). Compared with the placebo or standard care, nitazoxanide were associated with a similar risk of any adverse event (RD, -0.02; 95% CI: -0.07 to 0.03; P = 0.44). CONCLUSIONS: Although nitazoxanide can help virological eradication and is also tolerable, it does not provide additional clinical benefits. Based on these evidences, the use of nitazoxanide in the treatment of patients with COVID-19 is not recommended.

Fast one-pot microwave-assisted green synthesis of highly fluorescent plant-inspired S,N-self-doped carbon quantum dots as a sensitive probe for the antiviral drug nitazoxanide and hemoglobin

In this study, we report a one-pot, green, cost-efficient, and fast synthesis of plant-based sulfur and nitrogen self-co-doped carbon quantum dots (S,N-CQDs). By four-minutes microwave treatment of onion and cabbage juices as renewable, cheap, and green carbon sources and self-passivation agents, blue emissive S,N-CQDs have been synthesized (λex/λem of 340/418 nm) with a fluorescence quantum yield of 15.2%. A full characterization of the natural biomass-derived quantum dots proved the self-doping with nitrogen and sulfur. The S,N-CQDs showed high efficiency as a fluorescence probe for sensitive determination of nitazoxanide (NTZ), that recently found wide applicability as repurposed drug for COVID-19, over the concentration range of 0.25–50.0 μM with LOD of 0.07 μM. The nanoprobe has been successfully applied for NTZ determination in pharmaceutical samples with excellent % recovery of 98.14 ± 0.42. Furthermore, the S,N-CQDs proved excellent performance as a sensitive fluorescence nanoprobe for determination of hemoglobin (Hb) over the concentration range of 36.3–907.5 nM with a minimum detectability of 10.3 nM. The probe has been applied for the determination of Hb in blood samples showing excellent agreement with the results documented by a medical laboratory. The greenness of the developed probe has been positively investigated by different greenness metrics and software. The green character of the proposed analytical methods originates from the synthesis of S,N-CQDs from sustainable, widely available, and cheap plants via low energy/low cost microwave-assisted technique. Omission of organic solvents and harsh chemicals beside dependence on mix-and-read analytical approach corroborate the method greenness. The obtained results demonstrated the substantial potential of the synthesized green, safe, cheap, and sustainable S,N-CQDs for pharmaceutical and biological applications.

Safety and efficacy of four drug regimens versus standard-of-care for the treatment of symptomatic outpatients with COVID-19: A randomised, open-label, multi-arm, phase 2 clinical trial.

BACKGROUND: This exploratory study investigated four repurposed anti-infective drug regimens in outpatients with COVID-19. METHODS: This phase 2, single centre, randomised, open-label, clinical trial was conducted in South Africa between 3rd September 2020 and 23rd August 2021. Symptomatic outpatients aged 18-65 years, with RT-PCR confirmed SARS-CoV-2 infection were computer randomised (1:1:1:1:1) to standard-of-care (SOC) with paracetamol, or SOC plus artesunate-amodiaquine (ASAQ), pyronaridine-artesunate (PA), favipiravir plus nitazoxanide (FPV + NTZ), or sofosbuvir-daclatasvir (SOF-DCV). The primary endpoint was the incidence of viral clearance, i.e., the proportion of patients with a negative SARS-CoV-2 RT-PCR on day 7, compared to SOC using a log-binomial model in the modified intention-to-treat (mITT) population. FINDINGS: The mITT population included 186 patients: mean age (SD) 34.9 (10.3) years, body weight 78.2 (17.1) kg. Day 7 SARS-CoV-2 clearance rates (n/N; risk ratio [95% CI]) were: SOC 34.2% (13/38), ASAQ 38.5% (15/39; 0.80 [0.44, 1.47]), PA 30.3% (10/33; 0.69 [0.37, 1.29]), FPV + NTZ 27.0% (10/37; 0.60 [0.31, 1.18]) and SOF-DCV 23.5% (8/34; 0.47 [0.22, 1.00]). Three lower respiratory tract infections occurred (PA 6.1% [2/33]; SOF-DCV 2.9% [1/34]); two required hospitalisation (PA, SOF-DCV). There were no deaths. Adverse events occurred in 55.3% (105/190) of patients, including one serious adverse event (pancytopenia; FPV + NTZ). INTERPRETATION: There was no statistical difference in viral clearance for any regimen compared to SOC. All treatments were well tolerated. FUNDING: Medicines for Malaria Venture, with funding from the UK Foreign, Commonwealth and Development Office, within the Covid-19 Therapeutics Accelerator in partnership with Wellcome, the Bill and Melinda Gates Foundation, and Mastercard.

A guide to COVID-19 antiviral therapeutics: a summary and perspective of the antiviral weapons against SARS-CoV-2 infection.

Antiviral therapies are integral in the fight against SARS-CoV-2 (i.e. severe acute respiratory syndrome coronavirus 2), the causative agent of COVID-19. Antiviral therapeutics can be divided into categories based on how they combat the virus, including viral entry into the host cell, viral replication, protein trafficking, post-translational processing, and immune response regulation. Drugs that target how the virus enters the cell include: Evusheld, REGEN-COV, bamlanivimab and etesevimab, bebtelovimab, sotrovimab, Arbidol, nitazoxanide, and chloroquine. Drugs that prevent the virus from replicating include: Paxlovid, remdesivir, molnupiravir, favipiravir, ribavirin, and Kaletra. Drugs that interfere with protein trafficking and post-translational processing include nitazoxanide and ivermectin. Lastly, drugs that target immune response regulation include interferons and the use of anti-inflammatory drugs such as dexamethasone. Antiviral therapies offer an alternative solution for those unable or unwilling to be vaccinated and are a vital weapon in the battle against the global pandemic. Learning more about these therapies helps raise awareness in the general population about the options available to them with respect to aiding in the reduction of the severity of COVID-19 infection. In this 'A Guide To' article, we provide an in-depth insight into the development of antiviral therapeutics against SARS-CoV-2 and their ability to help fight COVID-19.