Drugs For Treatment Of COVID-19 Research Articles

10-camphor sulfonic acid: A simple and efficient organocatalyst to access anti-SARS-COV-2 Benzoxanthene derivatives

10-Camphor sulfonic acid (10-CSA) has gained popularity as an organocatalyst due to its broad range of solubility and user-friendliness. Affordable multicomponent reactions (MCRs) for the preparation of benzoxanthenes (4a-4 h) (5a-5i) are presented in this work. Extensive investigations and records have been conducted on the diverse biological features exhibited by xanthenes and benzoxanthenones, such as their antiviral, antibacterial, and anti-inflammatory capabilities.Using β-naphthol, dimedone, and aldehydes, we demonstrate a cost-effective and environmentally friendly catalytic method. Under ideal circumstances, the 10-CSA catalyzes one-pot reaction, procuring impressive amounts of benzoanthenes (85–95 %). All the synthesized compounds were characterized by 1H NMR and 13C NMR. A wide variety of suitable chemicals, simple work-up procedures, and solvent-free synthesis outperforms numerous existing methods for procuring biologically relevant benzoxanthene derivatives are some of the interesting features of this organocatalyzed bronsted acid process. Therefore this synthesis is industrially inevitable. Furthermore, computational studies such as molecular docking and ADMET data analysis were performed on a number of the synthesized benzoxanthene molecules. This has led to the identification of the most potent synthetic against the SARS-CoV-2 spike protein. Additionally, to mimic how medicinal compounds interact to target proteins, computational docking and dynamics techniques were used. These studies showed that, in terms of binding affinity and other crucial traits, 4a, 4b, and 5a are potential possibilities. Overall, the current study should be of great help in the development of benzoxanthene analogs which can be potential drugs for treatment of COVID-19.

Dual SARS-CoV-2 and MERS-CoV inhibitors from Artemisia monosperma: isolation, structure elucidation, molecular modelling studies, and in vitro activities.

The COVID-19 pandemic has spread throughout the whole globe, so it is imperative that all available resources be used to treat this scourge. In reality, the development of new pharmaceuticals has mostly benefited from natural products. The widespread medicinal usage of species in the Asteraceae family is extensively researched. In this study, compounds isolated from methanolic extract of Artemisia monosperma Delile, a wild plant whose grows in Egypt's Sinai Peninsula. Three compounds, stigmasterol 3-O-β-D-glucopyranoside 1, rhamnetin 3, and padmatin 6, were first isolated from this species. In addition, five previously reported compounds, arcapillin 2, jaceosidin 4, hispidulin 5, 7-O-methyleriodictyol 7, and eupatilin 8, were isolated. Applying molecular modelling simulations revealed two compounds, arcapillin 2 and rhamnetin 3 with the best docking interactions and energies within SARS-CoV-2 Mpro-binding site (-6.16, and -6.70 kcal mol-1, respectively). The top-docked compounds (2-3) were further evaluated for inhibitory concentrations (IC50), and half-maximal cytotoxicity (CC50) of both SARS-CoV-2 and MERS-CoV. Interestingly, arcapillin showed high antiviral activity towards SARS-CoV-2 and MERS-CoV, with IC50 values of 190.8 μg mL-1 and 16.58 μg mL-1, respectively. These findings may hold promise for further preclinical and clinical research, particularly on arcapillin itself or in collaboration with other drugs for COVID-19 treatment.

Computational insight of repurpose drug for treatment of COVID-19: a CDFT approach

Computational insight of repurpose drug for treatment of COVID-19: a CDFT approach

Dose-dependent Oxidative Damage of Molnupiravir (Antiviral Drug for Treatment of COVID-19) in Lung, Liver, Heart, and Kidney Tissues in Rats

Molnupiravir (MOL) is an orally absorbed prodrug of the ribonucleoside analogue N-hydroxycytidine, which has in vitro activity against several coronaviruses, including SARS-CoV-1 and 2. It remains to be seen whether long term MOL has serious side effects. The side effects of MOL, which was the first to be allowed for oral use during the pandemic process, are not yet fully known. In this study, it was aimed to investigate the the mechanisms of possible dose-dependent damage on liver, lung, heart, and kidney tissues. Fourty male Wistar albino rats were separated into four groups as Control, MOL10, MOL100, MOL1000. For five days, MOL (10-100-1000 mg/kg/day) was administered by oral gavaj. At the end of the five days rats were sacrificed and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB) levels in serum were measured. Collected tissues (liver, lung, heart, and kidney) were evaluated to the malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant state (TAS), and total oxidant state (TOS), and oxidative stress indexes (OSI) were calculated. MOL administration showed significant improvement in liver, heart, and kidney in rats (p<0.05). SOD activities which were decreased in the MOL group, while MDA level increased in the MOL groups compared to the control group in all tissue (p<0.05). ALT was increased in the MOL group compared to the control group (p<0.05). Increase of TOS and OSI is statistically significant, but TAS was decreased in the MOL group compared to the control group (p<0.05). MOL used in virus treatment is dose-dependently effective on the oxidant/antioxidant system in tissues. For this reason, the use of antioxidants may be beneficial to reduce tissue damage that may occur in the use of MOL.

Efficacy of Andrographis paniculata extract treatment in mild to moderate COVID-19 patients being treated with favipiravir: A double-blind, randomized, placebo-controlled study (APFaVi trial)

BackgroundWhile favipiravir had been the standard anti-SARS-CoV-3 drug for COVID-19 treatment in Thailand, the efficacy of favipiravir treatment is controversial. Andrographis paniculata extract (APE) inhibits viral entry, exhibits immunomodulatory effects, and proposes to have the potential for early-stage COVID-19 treatment. MethodsA randomized, double-blind, placebo-controlled trial was performed in Thailand during June - September 2021. Non-severe COVID-19 patients were randomized 1:1 to groups receiving 180 mg/day of APE plus favipiravir (APE-FPV group) or placebo plus favipiravir (placebo-FPV group). Efficacy in preventing disease progression to severe COVID-19 was assessed on day 4, using World Health Organization Clinical Progression Scale (WHOCPS) score and visual analog scale (VAS) for acute respiratory tract infection symptoms. ResultsOf 146 patients, there were 73 patients in each group. Non-deterioration of WHOCPS scores on day 4 was 98.63% versus 97.26% of patients in the APE-FPV and placebo-FPV groups (p = 1.000). No difference in supplemental oxygen, hospitalization, and death was shown in both groups. The oxygen supplemental was 4.11% in the placebo-FPV group. The interleukin (IL)-1β was significantly lower in the APE than in the placebo-FPV group throughout the study. We found no difference in virologic outcomes between groups and no substantial adverse events. ConclusionsAPE treatment did not demonstrate additional clinical and virological benefits in patients with mild to moderate COVID-19 being treated with favipiravir. Early reduction of IL-1β with APE may be advantageous in preventing cytokine storms in severe COVID-19 and requires further study.

Drugs for COVID-19 Treatment: A New Challenge.

COVID-19 infection is a new disease and our knowledge is limited; day in and day out more and more interesting yet diverse observations are reported by the different research groups from different corners of the world. So, there is an urgent requirement of the invention of some effective and efficient drugs that can carry out the end of the deadly viral infection. Throughout the world, there have been many efforts carried out in different labs to invent such a drug and also identifying any pre-existing drugs which can carry out the killing of the virus. In this review, an effort has been made to understand the potential drugs which can be used against the SARS-CoV-2 viral infection. Again, the strategies on the current and the future drug discovery mechanisms against the SARS-CoV-2 are also mentioned. The different drugs made and the drugs re-used and also the drugs which are in the making process in different research laboratories across the world are also mentioned. To combat this unexpected crisis, we still need some more efforts from the different scientific communities around the world for finding a cure against this viral infection and this is needed to be done for the prevention of more loss of human life.

Multi-omics characterization of RNA binding proteins reveals disease comorbidities and potential drugs in COVID-19

The COVID-19 has led to a devastating global health crisis, which emphasizes the urgent need to deepen our understanding of the molecular mechanism and identifying potential antiviral drugs. Here, we comprehensively analyzed the transcriptomic and proteomic profiles of 178 COVID-19 patients, ranging from asymptomatic to critically ill. Our analyses found that the RNA binding proteins (RBPs) were likely to be perturbed in infection. Interactome analysis revealed that RBPs interact with virus proteins and the viral interacting RBPs were likely to locate in central regions of human protein-protein interaction network. Functional enrichment analysis revealed that the viral interacting RBPs were likely to be enriched in RNA transport, apoptosis and viral genome replication-related pathways. Based on network proximity analyses of 299 human complex-disease genes and COVID-19-related RBPs in the human interactome, we revealed the significant associations between complex diseases and COVID-19. Network analysis also implicated potential antiviral drugs for treatment of COVID-19. In summary, our integrative characterization of COVID-19 patients may thus help providing evidence regarding pathophysiology and potential therapeutic strategies for COVID-19.

Structure-Based Design of a Dual-Targeted Covalent Inhibitor Against Papain-like and Main Proteases of SARS-CoV-2.

The two proteases, PLpro and Mpro, of SARS-CoV-2 are essential for replication of the virus. Using a structure-based co-pharmacophore screening approach, we developed a novel dual-targeted inhibitor that is equally potent in inhibiting PLpro and Mpro of SARS-CoV-2. The inhibitor contains a novel warhead, which can form a covalent bond with the catalytic cysteine residue of either enzyme. The maximum rate of the covalent inactivation is comparable to that of the most potent inhibitors reported for the viral proteases and covalent inhibitor drugs currently in clinical use. The covalent inhibition appears to be very specific for the viral proteases. The inhibitor has a potent antiviral activity against SARS-CoV-2 and is also well tolerated by mice and rats in toxicity studies. These results suggest that the inhibitor is a promising lead for development of drugs for treatment of COVID-19.

Notes From the Field: Dispensing of Oral Antiviral Drugs for Treatment of COVID-19 by Zip Code-Level Social Vulnerability - United States, December 23, 2021-August 28, 2022.

Equitable access to COVID-19 therapeutics is a critical aspect of the distribution program led by the U.S. Department of Health and Human Services (HHS).* Two oral antiviral products, nirmatrelvir/ritonavir (Paxlovid)† and molnupiravir (Lagevrio),§ received emergency use authorization (EUA) from the Food and Drug Administration (FDA) in December 2021, to reduce the risk for COVID-19-associated hospitalization and death for those patients with mild to moderate COVID-19 who are at higher risk for severe illness (1,2). HHS has been distributing these medications at no cost to recipients since their authorization. Data collected from provider sites during December 23, 2021-May 21, 2022, indicated substantial disparities in the population-adjusted dispensing rates in high social vulnerability (high-vulnerability) zip codes compared with those in medium- and low-vulnerability zip codes (3). Specifically, dispensing rates for the 4-week period during April 24-May 21, 2022, were 122 per 100,000 residents (19% of overall population-adjusted dispensing rates) in high-vulnerability zip codes compared with 247 (42%) in medium-vulnerability and 274 (39%) in low-vulnerability zip codes. This report provides an updated analysis of dispensing rates by zip code-level social vulnerability and highlights important intervention strategies.

The challenges and opportunities for the development of COVID-19 therapeutics and preparing for the next pandemic

The disease which is today known as COVID-19 is caused by severe acute respiratory. Syndrome coronavirus 2 (SARS-COV-2), was first reported in Wuhan, China in December 2019. The disease has claimed well over six million lives from over 500 million cases. Vaccine hesitancy militates against successful mass vaccination. There is the rapid emergence of new SARS-COV-2 variants, constituting a challenge to the effectiveness of vaccines. Moreover, none of the available vaccines offers 100% protection and even the protection offered is of short duration necessitating booster doses to be taken. Moving forward, the development of plant-based edible vaccines will be a remarkable strategic approach to overcome vaccine hesitancy and improve vaccine uptake. So far only about nine drugs for COVID-19 treatment have approvals by either or both the European Medicines Agency and the FDA. While drug repurposing to address the emerging need in the early period of the COVID-19 pandemic has been contextually very useful, investment in it remains relatively low for commercial reasons arising from patenting issues. Embarking on new drug discovery and development strategies targeting both the virus and host factors is a very appealing option. Targeting druggable targets that are present across viruses, particularly the coronaviruses, for drug discovery and development represents an important strategy for pandemic preparedness. Natural products are an important reservoir of chemical scaffolds with huge potential for the discovery of novel chemical entities for development of novel therapeutics. Phytopharming is an available technology that can be used for mass and accelerated production of therapeutic molecules that will be required within short periods of time as is the case in pandemic outbreaks. Nanotechnology provides excellent platforms for formulating multivalent vaccines and pan-viral medicines for the treatment of COVID-19. Taken together, this review discusses the potential for the development of therapeutics by using the tools of biocomputing, nanotechnology, and phytopharming for accelerated therapeutic development to achieve effective COVID-19 treatment and associated complications, including new and emerging variants of SARS-COV-2 and other viral pandemics that may emerge or re-emerge.

A Review on Dry Powder Inhalers of Repurposing Drugs for Covid-19 Treatment

Dry powder inhalation method has been convincing method for treating respiratory diseases as it directly delivers the drugs to the lungs in the form of fine powder. The novel coronavirus causes respiratory infection mainly targeting the ACE-2 receptors in the lower respiratory tract. Repurposing drugs like Remdesivir, Ivermectin, Favipiravir for treatment of covid-19 can be prepared as powders for inhalation. Covid-19 pandemic has increased the application of dry powder inhalation therapy of antiviral drugs. This review presents account on pulmonary drug delivery of repurposing drugs for treatment of Covid-19. Index Terms : — Dry powder inhalers, Novel Coronavirus, Repurposing drugs.

The Impact of the Coronavirus (COVID-19) Infection on the Drug-Metabolizing Enzymes Cytochrome P450s.

Coronaviruses cause disease in human and animals. In 2019 a novel coronavirus was first characterized in Wuhan, China. It causes acute respiratory disease and designated the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19. The COVID-19 spread to all cities of China, and in 2020 to the whole world. Patients with COVID-19 may recover without medical treatment. However, some patients need medical care. The Cytochrome p450s (CYP450s) are large superfamily of enzymes catalyze the metabolism of endogenous substrates and xenobiotics. CYP450s catalyze the biotransformation of 80% of the drug in clinical use. The CYP450 present in liver, lungs, intestine and other tissues. COVID-19 has been reported to decrease the activity of certain isoforms of CYP450s in an isoform specific manner. Furthermore, the COVID-19 infection decreases the liver functions including the drug clearance or detoxification medicated by the CYP450s. The healthcare providers should be aware of this disease-drug interaction when prescribing drugs for treatment of COVID-19 and other comorbidities.

Dispensing of Oral Antiviral Drugs for Treatment of COVID-19 by Zip Code-Level Social Vulnerability - United States, December 23, 2021-May 21, 2022.

The COVID-19 pandemic has highlighted and exacerbated long-standing inequities in the social determinants of health (1-3). Ensuring equitable access to effective COVID-19 therapies is essential to reducing health disparities. Molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid) are oral antiviral agents effective at preventing hospitalization and death in patients with mild to moderate COVID-19 who are at high risk* for progression to severe COVID-19 when initiated within 5 days of symptom onset. These medications received Emergency Use Authorization from the Food and Drug Administration (FDA) in December 2021† and were made available at no cost to recipients through the U.S. Department of Health and Human Services (HHS) on December 23, 2021. Beginning March 7, 2022, a series of strategies was implemented to expand COVID-19 oral antiviral access, including the launch of the Test to Treat initiative.§ Data from December 23, 2021-May 21, 2022, were analyzed to describe oral antiviral prescription dispensing overall and by week, stratified by zip code social vulnerability. Zip codes represented areas classified as low, medium, or high social vulnerability; approximately 20% of U.S. residents live in low-, 31% in medium-, and 49% in high-social vulnerability zip codes.¶ During December 23, 2021-May 21, 2022, a total of 1,076,762 oral antiviral prescriptions were dispensed (Lagevrio = 248,838; Paxlovid = 827,924). Most (70.3%) oral antivirals were dispensed during March 7-May 21, 2022. During March 6, 2022-May 21, 2022, the number of oral antivirals dispensed per 100,000 population increased from 3.3 to 77.4 in low-, from 4.5 to 70.0 in medium-, and from 7.8 to 35.7 in high-vulnerability zip codes. The number of oral antivirals dispensed rose substantially during the overall study period, coincident with the onset of initiatives to increase access. However, by the end of the study period, dispensing rates in high-vulnerability zip codes were approximately one half the rates in medium- and low-vulnerability zip codes. Additional public health, regulatory, and policy efforts might help decrease barriers to oral antiviral access, particularly in communities with high social vulnerability.

Application of Monoclonal Antibody Drugs in Treatment of COVID-19: a Review.

Coronavirus infection can have various degrees of severity and outcomes. In some cases, it causes excessive production of pro-inflammatory cytokines, a so-called cytokine storm, leading to acute respiratory distress syndrome. Unfortunately, the exact pathophysiology and treatment, especially for severe cases of COVID-19, are still uncertain. Results of preliminary studies showed that immunosuppressive therapy, such as interleukin (IL)-6, IL-1, and TNF-α antagonists commonly used in rheumatology, can be considered as treatment options for COVID-19, especially in severe cases. The review focused on the most common and currently studied monoclonal antibody drugs, as well as up-to-date data on the pathogenesis of COVID-19, host immune response against SARS-CoV-2 and its association with cytokine storm. It also covered effects of interleukin (IL)-6, IL-1, and TNF-α blockers on the course of coronavirus infection and outcome in patients treated for the main autoimmune disease and subsequently infected with COVID-19.

Quantitative analysis of favipiravir and hydroxychloroquine as FDA-approved drugs for treatment of COVID-19 using synchronous spectrofluorimetry: application to pharmaceutical formulations and biological fluids.

Coronavirus disease 2019 (COVID‐19) is a contagious viral infection caused by coronavirus 2 (SARS‐CoV‐2) that causes severe acute respiratory syndrome. It has ravaged several countries and burdened many healthcare systems. As the process of authorizing a novel treatment for human use is extensive and involves multiple phases to obtain safety information and identify potential concerns. Therefore, the fastest and easiest choice was to use United States Food and Drug Administration (US FDA)‐approved drugs such as favipiravir and hydroxychloroquine. For the simultaneous estimation of both medications, a simple synchronous spectrofluorimetric approach was established in which both drugs were measured at 372 and 323 nm, respectively in the presence of each other without interference at Δλ 60 nm. The effect of various experimental conditions on synchronous fluorescence intensities were thoroughly investigated and optimized. The maximum synchronous fluorescence intensities were obtained at pH 5.4 using acetate buffer (0.2 M, 0.5 ml) and ethanol as a diluent. Excellent linearity ranges were obtained using 1.0–18.0 ng/ml and 10.0–120.0 ng/ml for favipiravir and hydroxychloroquine, respectively. The approach exhibited high sensitivity with detection limits down to 0.25 ng/ml and 1.52 ng/ml and quantitation limits down to 0.77 ng/ml and 4.62 ng/ml, respectively. Spiking human plasma samples with the studied drugs yielded high % recoveries, allowing a significant bioanalytical application. Moreover, the method was validated according to International Conference on Harmonization guidelines and further applied to commercial pharmaceutical preparations with good results.

How the Innate Immune System of the Blood Contributes to Systemic Pathology in COVID-19-Induced ARDS and Provides Potential Targets for Treatment.

Most SARS-CoV-2 infected patients experience influenza-like symptoms of low or moderate severity. But, already in 2020 early during the pandemic it became obvious that many patients had a high incidence of thrombotic complications, which prompted treatment with high doses of low-molecular-weight heparin (LMWH; typically 150-300IU/kg) to prevent thrombosis. In some patients, the disease aggravated after approximately 10 days and turned into a full-blown acute respiratory distress syndrome (ARDS)-like pulmonary inflammation with endothelialitis, thrombosis and vascular angiogenesis, which often lead to intensive care treatment with ventilator support. This stage of the disease is characterized by dysregulation of cytokines and chemokines, in particular with high IL-6 levels, and also by reduced oxygen saturation, high risk of thrombosis, and signs of severe pulmonary damage with ground glass opacities. The direct link between SARS-CoV-2 and the COVID-19-associated lung injury is not clear. Indirect evidence speaks in favor of a thromboinflammatory reaction, which may be initiated by the virus itself and by infected damaged and/or apoptotic cells. We and others have demonstrated that life-threatening COVID-19 ARDS is associated with a strong activation of the intravascular innate immune system (IIIS). In support of this notion is that activation of the complement and kallikrein/kinin (KK) systems predict survival, the necessity for usage of mechanical ventilation, acute kidney injury and, in the case of MBL, also coagulation system activation with thromboembolism. The general properties of the IIIS can easily be translated into mechanisms of COVID-19 pathophysiology. The prognostic value of complement and KKsystem biomarkers demonstrate that pharmaceuticals, which are licensed or have passed the phase I trial stage are promising candidate drugs for treatment of COVID-19. Examples of such compounds include complement inhibitors AMY-101 and eculizumab (targeting C3 and C5, respectively) as well as kallikrein inhibitors ecallantide and lanadelumab and the bradykinin receptor (BKR) 2 antagonist icatibant. In this conceptual review we discuss the activation, crosstalk and the therapeutic options that are available for regulation of the IIIS.

COVID-19 in Hospitalised Children and Adolescents: Review of the First Pandemic Year at Vilnius University Hospital Santaros Klinikos.

Summary.Background.Since the start of the pandemic with SARS-CoV-2 virus, very little data was known about clinical features and outcomes of COVID-19 in children and adolescents not only in Lithuania, but also in other European countries. This study was started in collaboration with 82 participating healthcare institutions across 25 European countries, using a well-established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet). This multinational, multicentre cohort study was performed during the first wave of the pandemic, between April 1 and April 24, 2020. Each participating country was allowed to continue further research individually encompassing brighter time limits and using the same methodology. We present here data of children hospitalised at Vilnius University Hospital Santaros Klinikos (VUH SK) during the first year of the pandemic.Materials and methods.We included all paediatric patients with PCR confirmed SARS-CoV-2 infection who were hospitalised at VUH SK. The study was performed between March 12, 2020 and March 12, 2021. A standardised data collection spreadsheet was used to record epidemiological, clinical and treatment data.Results.A total of 104 patients were included in the study. The median age of participants was 5 years (IQR 1.0-11.0, range 0-17 years). Males accounted for 50 (48%) of all patients. The average duration of hospitalisation was 3 days. Ten (9.6%) patients had pre-existing medical conditions. Among all hospitalised patients 16 (15%) were asymptomatic, 5 (4.8%) were treated in intensive care unit (ICU). The most common symptoms among COVID-19 patients were pyrexia 71 (68%) followed by upper respiratory tract infection 49 (47%) and gastrointestinal symptoms 33 (32%). Among the entire cohort only 3 (3%) patients required oxygen support, but none of them was started on continuous positive airway pressure (CPAP), mechanical ventilation or extracorporeal membrane oxygenation (ECMO). None of the patients admitted to ICU needed inotropic support. There was no fatal outcome.Conclusions.Our data indicate that COVID-19 may affect children of any age. The COVID-19 disease was usually mild in hospitalized children and adolescents. The most common clinical findings of COVID-19 were pyrexia and symptoms of upper respiratory tract infection. Severe COVID-19 disease cases when oxygen support or treatment in ICU was required were very rare. No patient received antiviral drugs for Covid-19 treatment. There was no fatal outcome due to COVID-19 in our study population.

Experience in Using Antiviral Agents for the Treatment of Novel Coronavirus Infection (COVID-19) in Kyrgyzstan

The national clinical guidelines for the treatment of novel coronavirus infection (COVID-19) are the main source of information and the reference point for clinical decision-making by healthcare professionals in the Kyrgyz Republic. The recommendations presented in these documents are largely based on data from real clinical practice, but the efficacy and safety of a number of antiviral agents, the indications for which have been expanded to include COVID-19 treatment, remain unclear.The aim of the study was to conduct a retrospective pharmacoepidemiological analysis of lopinavir+ritonavir use in hospitals in the Kyrgyz Republic for the treatment of COVID-19 during the period from March until April 2020.Materials and methods: the paper describes a retrospective study of 145 medical records of patients with confirmed COVID-19 who were hospitalized in infectious disease departments/hospitals of the Kyrgyz Republic. Statistical processing was performed using Microsoft Excel 2017.Results: between 16 March 2020 and 25 April 2020, 145 patients were prescribed lopinavir+ritonavir at a dose of 200 mg + 50 mg, 2 tablets twice a day—in line with the dosage regimen recommended by the national guideline. The national guideline recommended the treatment duration of 10 days, while the actual treatment duration was 1–12 days (5.5 days on average) depending on the tolerability of the drug. The use of the drug was accompanied by adverse drug reactions (ADRs) in 78 patients (53.8%), and caused deterioration in the general condition of 73 of these patients (94.8%) which resulted in discontinuation of the drug. The most common ADRs were nausea, vomiting, diarrhoea, decreased appetite, yellowness of the skin, and, according to laboratory studies, an increase in serum levels of bilirubin, creatinine, glucose, aspartate aminotransferase and amylase activity. A retrospective assessment of the causal relationship probability according to the Naranjo scale showed an interrelation between the use of lopinavir+ritonavir and ADR development.Conclusions: the use of the lopinavir+ritonavir drug in COVID-19 patients led to deterioration of their general condition, which was severe in some cases. The data obtained indicate that the use of this drug for COVID-19 treatment is clinically unreasonable and irrational. Lopinavir+ritonavir was excluded from subsequent revisions of the clinical guidelines for the diagnosis and treatment of COVID-19 in the Kyrgyz Republic.

IL-1 and IL-6 inhibition affects the neutralising activity of anti-SARS-CoV-2 antibodies in patients with COVID-19.

IL-1 and IL-6 inhibition affects the neutralising activity of anti-SARS-CoV-2 antibodies in patients with COVID-19.

Evaluation of the Effect of Outdated Drugs for Treatment of COVID-19

Evaluation of the Effect of Outdated Drugs for Treatment of COVID-19