Development and validation of method for analysis of favipiravir and remdesivir in volumetric absorptive microsampling with ultra high-performance liquid chromatography-tandem mass spectrophotometry.

Favipiravir and remdesivir are drugs to treat COVID-19. This study aims to find an optimum and validated method for simultaneous analysis of favipiravir and remdesivir in Volumetric Absorptive Microsampling (VAMS) by Ultra High-Performance Liquid Chromatography-Tandem Mass Spectrophotometry. The use of VAMS can be an advantage because the volume of blood is small and the sample preparation process is simple. Sample preparation was done by precipitation of protein using 500 µL of methanol. Analysis was carried out by ultra high-performance liquid chromatography-tandem mass spectrophotometry with ESI+ and MRM with m/z 157.9 > 112.92 for favipiravir, 603.09 > 200.005 for remdesivir, and at m/z 225.968 > 151.991 for acyclovir as the internal standard. The separation was carried out using an Acquity UPLC BEH C18 column (100 × 2.1 mm; 1.7 m), 0.2% formic acid-acetonitrile (50:50), flow rate was 0.15 mL/min, and column temperature was 50°C. The analytical method has been validated with the requirements issued by the Food and Drug Administration (2018) and European Medicine Agency (2011). The calibration range of favipiravir is 0.5-160 µg/mL and 0.002-8 µg/mL for remdesivir.

Characteristics of liver injury in cases of COVID-19.

In novel coronavirus disease 2019 (COVID-19), liver injury was found at a high rate, and reports from outside Japan revealed that such injury was related to severity. We examined the characteristics of liver injury in 15 cases of COVID-19. Thirteen of these patients received antiviral therapy, such as favipiravir, remdesivir, and hydroxychloroquine. Liver injury was observed in eight cases at admission for COVID-19. The hepatic CT attenuation values at admission were significantly lower in nine patients who developed liver damage or showed its exacerbation during the treatment than in the remaining patients. Drug-induced liver injury due to antiviral drug was suspected in six cases. Liver injury due to COVID-19 may be related to low hepatic CT attenuation values and be modified by antiviral drugs.Copyright © 2021 The Japan Society of Hepatology.

Outcome of COVID-19 on Indian patients with cancer: A multicenter, retrospective study

Background: Managing patients with cancer during the coronavirus disease 2019 (COVID-19) pandemic has been challenging. Disruptions in cancer management have been observed due to cancellation of treatment, issues related to commuting, and dearth of health-care workers. Objective(s): This study was conducted during the first wave of the COVID-19 pandemic and was aimed at evaluating the 30-day all-cause mortality among patients with cancer and COVID-19 infection and the factors affecting it. Material(s) and Method(s): In this retrospective study, we collected secondary data from nine tertiary care centers in South India over a period of 10 months from March to Dec 2020. Patients across all age groups with histopathologically confirmed diagnosis of cancer who were affected by COVID-19 during their evaluation or treatment were included in the study. The primary outcome variables of the present study were 30-day all-cause mortality, cancer outcomes, and COVID-19 outcomes. Result(s): A total of 206 patients were included. Median age of the cohort was 55.5 years, and the male-To-female ratio was 1:1.03. The 30-day mortality rate was 12.6%. Twenty-Two patients (10.7%) had severe COVID-19 infection at the initial presentation. Predictors for severe pneumonia at the initial presentation were incomplete remission at the time of COVID-19 diagnosis and palliative intent of treatment. Severe pneumonia at the initial presentation, diagnosis of COVID-19 on or before August 2020, and need for ventilator support were associated with increased mortality. Conclusion(s): Severity of infection at the initial presentation, cancer status, and the intent of cancer treatment impact COVID-19 outcomes in patients with cancer.Copyright © 2022 Iranian Society of Ophthalmology. All rights reserved.

Improving the Dissolution Rate and the Bioavailability of Favipiravir by Solid Dispersion with Curcumin

Favipiravir is an anti-viral agent that inhibits RNA-dependent RNA polymerase of several RNA viruses and is approved for the treatment of influenza in Japan. It has a role as an antiviral drug, an anti-coronaviral (COVID-19) agent but the poor solubility of the favipiravir in the aqueous media of the human body cause a reduction in the effectiveness and bioavailability. In the current work, the favipiravir was formulated for the first time as solid dispersed system with curcumin to improve dissolution property and antiviral activity during treatment of Covid-19. Binary and ternary mix of favipiravir and curcumin with/without soluplus were prepared and characterized by Differential Scanning Calorimetry (DSC), Powder X-ray Diffractometry (PXRD) and Fourier Transform Infrared Spec-troscopy (FTIR) and subjected to the dissolution test by apparatus I according to the European Pharma-copeia. The antiviral activity was measured by its cytotoxicity against A549-hACE2 cells. The results re-vealed that there was a reduction in the crystallinity of both binary and ternary mixtures with an en-hancement of the dissolution in comparison with the pure drug which accompanied by an improvement in the antiviral activity which is promising results that need further .Copyright © 2023, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.

Pharmacokinetic evaluation of drug-drug interactions in the treatment of COVID-19.

Objective: The COVID-19 pandemic, which started in Wuhan, China and affected the whole world, still represents a unique global challenge with its contagiousness and lethality. The symptoms of COVID-19 patients may differ depending on the severity of the disease. According to the report published by the Ministry of Health Coronavirus Research Advisory Board on the diagnosis, treatment and control of COVID-19, drug combination therapy (hydroxychloroquine, lopinavir / ritonavir and favipiravir) is recommended by health authorities. Drug-drug interaction is a possible situation as a result of simultaneous use of these drugs, which are metabolized by cytochrome P 450 enzymes (CYP), which are mostly found in the liver, with some other drugs. In this review, we aimed to show the pharmacokinetic drug-drug interactions of the drugs used in the treatment of COVID-19, especially by indicating the metabolism pathways. Result and Discussion: The COVID-19 pandemic adversely affects social life, economic and financial markets worldwide. Appropriate treatment protocols are of great importance but taking drug-drug interactions into account in treatment practices prevents unwanted results in patient treatment.Copyright © 2021 University of Ankara. All rights reserved.

Clinical profile and outcomes of COVID-19 infection during the first wave in children with hematological illnesses and cancer: An observational study from a tertiary care center in North India

Background: Patients with cancer are at a higher risk of getting infected with the severe acute respiratory syndrome coronavirus 2 owing to their immunocompromised state. Providing care to these patients amidst the first wave of the coronavirus disease-2019 (COVID-19) pandemic was extremely challenging. Objective(s): This study was aimed at evaluating the clinical profile and disease-related outcomes of pediatric patients with hematological illnesses and cancer. Material(s) and Method(s): This retrospective study was conducted at a tertiary care center in North India during the first wave of the pandemic from March 2020 to December 2020. Children aged up to 18 years, who were treated for a hematological illness or malignancy or underwent hematopoietic stem cell transplantation (HSCT) and tested positive for COVID-19 regardless of symptoms were included in the study. Baseline demographic data related to the age, diagnosis, treatment status, and chemotherapy protocol used were collected. Outcomes including the cure rates, comorbidities, and sequelae were recorded. Result(s): A total of 650 tests for COVID-19 were performed for 181 children;22 patients were found to be COVID-19 positive. The most common diagnosis was acute leukemia (63.6%). None of the patients developed COVID-19 pneumonia. The majority of patients had asymptomatic infection and were managed at home. Among those with a symptomatic infection, the most common symptoms were fever and cough. A total of 3 (13.6%) patients needed oxygen therapy, one developed multisystem inflammatory syndrome of children leading to cardiogenic shock. Three patients required intensive care or respiratory support;all the patients had favorable clinical outcomes. The median time from the onset of COVID-19 to a negative result on the reverse transcription-polymerase chain reaction test was 21.3 days. Cancer treatment was modified in 15 patients (68.2%). Conclusion(s): Our results suggest that children with hemato-oncological illnesses rarely experience severe COVID-19 disease. The impact of the first wave of COVID-19 primarily manifested as disruptions in the logistic planning and administration of essential treatment to these children rather than COVID-19 sequelae.Copyright © 2021 Cancer Research, Statistics, and Treatment Published by Wolters Kluwer - Medknow.

Drug utilization study in patients affected with COVID-19 in a dedicated COVID hospital

Background: There exists a treatment dilemma regarding the optimal and effective use of therapeutic drugs (hydroxychloroquine/chloroquine/azithromycin) for COVID-19. Furthermore, with changing guidelines, the data on drug utilization patterns across India are limited. Hence, this study was conducted to assess the prescription pattern and drug utilization trends in COVID-19 patients with the aim to study the drug utilization pattern in patients affected with COVID-19 in a dedicated COVID-19 hospital. Aims and Objectives: The objectives of the study are as follows: (1) To study drug utilization patterns according to the severity of the disease. (2) To study the prevalence of adverse drug reactions (ADRs). Materials and Methods: Data were collected retrospectively from 100 medical records of patients 18 years irrespective of sex admitted in the COVID ward and ICU of a dedicated COVID hospital from May to August 2020. Pregnant and lactating women were excluded from the study. ADRs reported were also analyzed. Results: About 71% were mild in this study, 18% were moderate, and 11% were severe COVID-19 patients. Overall, the most common drugs prescribed were multivitamins, followed by pantoprazole, paracetamol, and azithromycin. Hydroxychloroquine was prescribed in 22%, favipiravir in 7%, and remdesivir in 3% of cases. The majority of moderate COVID patients received injectables piperacillin-tazobactam, methylprednisolone, and enoxaparin. The mean number of medications, duration of admission, and number of days on oxygen were higher and significant in moderate compared to mild and severe COVID patients. Overall, ADRs were encountered in 9% of cases. Conclusion: The prescribed pattern of drugs was by the national standard guidelines. Multivitamins, followed by pantoprazole, paracetamol, and azithromycin dominated the prescription pattern. Polypharmacy was encountered, which needs to be addressed for the rational use of drugs.

Personalized approach to the management of a patient with COVID-19 with a complicated comorbid background

The aim of the work is to form the principles of a personalized approach to the management of patients with COVID-19 with a complicated comorbid background. Material and methods. The article describes a clinical case of successful recovery of an 87-year-old patient from a new coronavirus infection COVID-19, complicated by pneumonia involving 36% of the lung parenchyma area. Along with age, the situation was aggravated by the comorbid status of the patient: the presence of chronic lymphocytic leukemia, hypertension, mechanical prostheses of the mitral and aortic valves, postinfarction cardiosclerosis, paroxysmal atrial fibrillation, type 2 diabetes mellitus, stage 4 CKD, anemic syndrome, and subclinical hypothyroidism. Results. The C-reactive protein level at admission was 114.46 mg/L. The patient refused hospitalization. Baricitinib 4 mg, favipiravir according to the scheme, vitamin D 2000 units were prescribed for the previously taken therapy. Already after 3 days, C-reactive protein decreased by 4.6 times, and by the 8th day by 15.5 times and amounted to 7.38 mg/ml. The temperature returned to normal on day 2 from the start of baricitinib. In dynamics, a decrease in creatinine level to 177.0 mumol/l was noted, the glomerular filtration rate increased to 30 ml/min/1.73 m2, which corresponded to stage 3b of CKD (a pronounced decrease in glomerular filtration rate). Conclusion. Despite the age of the patient, many comorbidities, each of which could be fatal, the timely use of baricitinib on an outpatient basis made it possible to stop the progressive course of the disease.Copyright © Eco-Vector, 2023. All rights reserved.

Acute urticaria with Angioedema in a patient with COVID-19 pneumonia: Favipiravir side effect or a rare cutaneous manifestation

Introduction: Coronavirus disease 2019 (COVID-19) has caused thousands of deaths since it was declared as a pandemic. Recently it continues to be one of the most followed topics in the world in terms of its course and treatment. Favipiravir is a broad-spectrum anti-viral agent that has been shown to be effective against various Coronaviruses in vitro. However, as with any drug use, side effects may develop with the use of favipravir treatment. Case Report: We reported a 55-year-old female patient with acute urticarial with angioedema whom had COVID-19 pneumonia. She had no history of allergy, atopy, previous similar episodes or family history of hereditary angioedema. There is no drug or food consumption that may be suspicious in terms of allergy described by the patient other than favipravir. Conclusion(s): As far as we know, it is the first case reported from our country. Since there is no specific examination for differential diagnosis, we cannot distinguish as a rare side effect due to favipiravir treatment or COVID-19 cutaneous manifestation. As a result, studies involving more cases of COVID-19 skin findings are needed.© Copyright 2020 by Emergency Physicians Association of Turkey.

Analysis data of mechanism of drugs recommended for the treatment of COVID-19

The purpose of this review is to analyze the data of scientific articles on medicines indicated as etiotropic and approved for outpatient use within the framework of temporary methodological recommendations for the prevention, diagnosis and treatment of a new coronavirus infection in the Russian Federation. Material and methods. A systematic search of literature was carried out on the databases MEDLINE, PubMed, Cochrane Library, GHL, OpenGrey, ICTRP and ClinicalTrials.gov until April 2021. 37 779 articles were indexed in the ScienceDirect database (keywords: SARS-CoV-2), of which (pre-press) - 2023 (2), 2022 (69), published in 2021 (19 642 articles), in 2020 (12,966 articles). The search was carried out using the following keywords: Favipiravir - 1622 publications, Umifenovir - 387 publications, which indicates a high interest in the problem of new coronavirus infection in general and its drug (etiotropic) therapy, in particular. Results. The conducted analysis demonstrates that drugs based on favipiravir have a larger number of studies proving its effectiveness in different clinical groups of patients with COVID-19, while it is important to note the breadth of the geography of published works, which allows us to speak about the reproducibility of the results. Drugs from this group have a direct antiviral effect with the studied target of action (i.e., most likely, the principle of etiotropic therapy is implemented). Conclusion. The search for new drugs, as well as the expansion of information about the mechanisms of action of previously known molecules, is the basis for the development of COVID-19 therapy regimens with maximum efficiency and safety.Copyright © 2021 Sovero Press Publishing House. All rights reserved.

A Review of the Analytical Methods for the Determination of Favipiravir

Favipiravir is, an antiviral agent, used to treat diseases caused by RNA viruses like Ebola virus, SARS-CoV-2, Influenza virus, Polio measles etc. The prodrug Favipiravir enters the infected cells through endocytosis and undergo metabolism to become an active drug. An active form of Favipiravir selectively targets the catalytic domain of RNA-dependent RNA polymerase and then interrupts the nucleotide incorporation process during viral RNA replication. This dysregulation of viral RNA replication results in mutations where the replacement of guanine by adenine and cytosine by thymine occurs. This ultimately induces destructive mutagenesis in RNA viruses. Currently, Favipiravir is available in tablet and intravenous dosage forms. The following analytical methods have been carried over for Favipiravir: UV, HPLC, LC-MS/MS, Spectrofluorometric method, and HPTLC-densitometric techniques are reported as per literature. The present paper illustrates the review of analytical methods which involve the estimation of Favipiravir in bulk or dosage form. The review also describes the scope and limitations of many published analytical methods for the analysis of Favipiravir. This detailed review article will be of great help to the researcher who is working on Favipiravir.Copyright © 2023 Society of Pharmaceutical Sciences and Research. All rights reserved.

Case report: Favipiravir-induced bluish corneal discoloration in infant with COVID-19.

This report describes a case of a male infant diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who was prescribed favipiravir therapy. The mother noticed a discoloration of the child's eyes within 18 h of therapy, and the cornea returned to normal color within 5 days of medication cessation. This case report highlights the need for monitoring of favipiravir therapy in children due to the potential side effect of corneal discoloration, which has not yet had its long-term effects identified.

Revealing the structural and molecular interaction landscape of the favipiravir-RTP and SARS-CoV-2 RdRp complex through integrative bioinformatics: Insights for developing potent drugs targeting SARS-CoV-2 and other viruses.

BACKGROUND: The global research community has made considerable progress in therapeutic and vaccine research during the COVID-19 pandemic. Several therapeutics have been repurposed for the treatment of COVID-19. One such compound is, favipiravir, which was approved for the treatment of influenza viruses, including drug-resistant influenza. Despite the limited information on its molecular activity, clinical trials have attempted to determine the effectiveness of favipiravir in patients with mild to moderate COVID-19. Here, we report the structural and molecular interaction landscape of the macromolecular complex of favipiravir-RTP and SARS-CoV-2 RdRp with the RNA chain. METHODS: Integrative bioinformatics was used to reveal the structural and molecular interaction landscapes of two macromolecular complexes retrieved from RCSB PDB. RESULTS: We analyzed the interactive residues, H-bonds, and interaction interfaces to evaluate the structural and molecular interaction landscapes of the two macromolecular complexes. We found seven and six H-bonds in the first and second interaction landscapes, respectively. The maximum bond length is 3.79 Å. In the hydrophobic interactions, five residues (Asp618, Asp760, Thr687, Asp623, and Val557) were associated with the first complex and two residues (Lys73 and Tyr217) were associated with the second complex. The mobilities, collective motion, and B-factor of the two macromolecular complexes were analyzed. Finally, we developed different models, including trees, clusters, and heat maps of antiviral molecules, to evaluate the therapeutic status of favipiravir as an antiviral drug. CONCLUSIONS: The results revealed the structural and molecular interaction landscape of the binding mode of favipiravir with the nsp7-nsp8-nsp12-RNA SARS-CoV-2 RdRp complex. Our findings can help future researchers in understanding the mechanism underlying viral action and guide the design of nucleotide analogs that mimic favipiravir and exhibit greater potency as antiviral drugs against SARS-CoV-2 and other infectious viruses. Thus, our work can help in preparing for future epidemics and pandemics.

Synchronous spectrofluorimetric determination of favipiravir and aspirin at the nano-gram scale in spiked human plasma; greenness evaluation.

Favipiravir and aspirin are co-administered during COVID-19 treatment to prevent venous thromboembolism. For the first time, a spectrofluorometric method has been developed for the simultaneous analysis of favipiravir and aspirin in plasma matrix at nano-gram detection limits. The native fluorescence spectra of favipiravir and aspirin in ethanol showed overlapping emission spectra at 423 nm and 403 nm, respectively, after excitation at 368 nm and 298 nm, respectively. Direct simultaneous determination with normal fluorescence spectroscopy was difficult. The use of synchronous fluorescence spectroscopy for analyzing the studied drugs in ethanol at Δλ = 80 nm improved spectral resolution and enabled the determination of favipiravir and aspirin in the plasma matrix at 437 nm and 384 nm, respectively. The method described allowed sensitive determination of favipiravir and aspirin over a concentration range of 10-500 ng/mL and 35-1600 ng/mL, respectively. The described method was validated with respect to the ICH M10 guidelines and successfully applied for the simultaneous determination of the mentioned drugs in pure form and in the spiked plasma matrix. Moreover, the compliance of the method with the concepts of environmentally friendly analytical chemistry was evaluated using two metrics, the Green Analytical Procedure Index and the AGREE tool. The results showed that the described method was consistent with the accepted metrics for green analytical chemistry.

A dispersion-corrected DFT calculation on encapsulation of favipiravir drug used as antiviral against COVID-19 into carbon-, boron-, and aluminum-nitride nanotubes for optimal drug delivery systems combined with molecular docking simulations.

Favipiravir (FAV) (6-fluoro-3-oxo-3,4-dihydropyrazine-2-carboxamide) is one of the most effective antiviral drugs which is cited for action against RNA-viral infections of COVID-19. In this study, density functional theory (DFT) calculations were used to investigate three nanotubes (NTs) with FAV drug as delivery systems. The encapsulated systems (ESs) consist of FAV drug inside carbon-carbon, aluminum nitride, and boron nitride. At B3LYP-D/6-31G(d,p) and CPCM/B3LYP-D/6-31G(d,p), the optimization of NTs, FAV, and its tautomeric forms and six ESs was investigated in gas and water environments. Five tautomeric forms of FAV were investigated, two keto forms (K1 and K2) and three enol forms (E1, E2, and E3). The results revealed that E3 and K2 isomeric forms represented the most stable structures in both media; thus, these two forms were encapsulated into the NTs. The stability and the synthesis feasibility of NTs have been proven by calculating their interaction energies. Non-covalent interactions (NCIs) were investigated in the ESs to show the type of NCI with the molecular voids. The binding energies, thermochemical parameters, and recovery times were investigated to understand the mechanism of FAV encapsulation and release. The encapsulated AlNNT systems are more favorable than those of BNNTs and CNTs in gas and aqueous environments with much higher binding energies. The quantum theory of atoms in molecules (QTAIM) and recovery time analysis revealed the easier releasing of E3 from AlNNT over K2 form. Based on molecular docking simulations, we found that E3 and K2 FAV forms showed a high level of resistance to SARS-CoV-6M3M/6LU7/6W9C proteases. Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-023-02182-4.

Fluvoxamine with bromhexine combination to prevent clinical deterioration in SARS-CoV-2

Introduction/Aim: We conducted an open label, randomized, controlled trial to assess whether fluvoxamine combined with bromhexine, given during mild to moderate SARS-CoV-2 illness, prevented clinical deterioration due to their proposed immune modulatory effects. Method(s): Participants had confirmed SARS-CoV-2 infection, experiencing mild to moderate symptoms and oxygen saturation of >=92%. Participants were randomly assigned to receive fluvoxamine (100 mg days 1 and 2, followed by 150 mg daily till day 14) with bromhexine (FLU/BRO) (16 mg daily till day 10) or favipiravir alone (FAV) (3600 mg day 1 followed by 1600 mg daily till day 5). Primary outcome was clinical deterioration within 30 days of randomization defined as shortness of breath or hospitalization for shortness of breath or pneumonia and oxygen saturation >=92%, on room air or need for supplemental oxygen to achieve oxygen saturation of >=92%. Result(s): 158 participants were randomized (average age 50 years (range 18-68 years);68 [43%] women), and 142 (89%) completed the trial. 0/78 participants experience clinical deterioration with FLU/BRO and 18/64 patients with FAV. TNF-alpha, IL-6 IL-8 and IL-1beta levels were significantly (p < 0.005) reduced with FLU/BRO compared to FAV at day 3, 5, 7 and 14. 0/78 participants had long COVID symptoms with FLU/BRO compared to 32/64 (50%) with FAV (p < 0.005). One serious (clumsiness or unsteadiness) and 10 other adverse events were reported with FLU/BRO compared to 5 serious and 12 other adverse events with FAV. Conclusion(s): Results suggest there was significantly less clinical deterioration in symptomatic COVID-19 participants treated with FLU/BRO.

Does high dose favipiravir improve COVID-19 pneumonia patients' outcome? - A retrospective cohort study

Introduction: Human Coronavirus Disease COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2). Favipiravir is an oral, broad-spectrum inhibitor of viral RNA-dependent RNA polymerase. The Malaysian national consensus guidelines recommended standard favipiravir dosage (1800mg BD day 1 and 800mg BD for 5-14days) to treat COVID-19 pneumonia, which was complied by HSNZ since January 2021. A study in Thailand noted better prognosis in patients given higher favipiravir doses. The Hospital Sultanah Nur Zahirah infectious disease team applied compassionate treatment, with increased doses (>45mg/kg/day) since June 2021. This study aims to compare the clinical deterioration of patients receiving high or standard doses of favipiravir. Method(s): This is a retrospective cohort study. Electronic medical record of 122 patients admitted during January to August 2021 were selected. Clinical deterioration is defined by occurrence of hypoxia requiring increased oxygenation throughout admission. Analysis via chi-square and Man-Whitney U test were done to compare among two groups. Result(s): The mean age is 57.4+/-16.3 y/o, with 65 (53.3%) men, and 117 (95.9%) Malays. Median day of illness upon admission is 5 (IQR: 3-6), 72(59%) patients have underlying comorbidities. There is no significant difference in baseline characteristics among both groups. Chi-square analysis of occurrence hypoxic deterioration shows no significant difference. However, significant difference is noted in days to deterioration (p<0.001) with high dose 6 days (IQR: 5-7.75), vs standard dose 1 days (IQR: 1-3). Conclusion(s): Among COVID-19 category 4 patients, high dose favipiravir shows superiorly in delaying clinical deterioration, however no significant difference in occurrence of deterioration.

Investigation of antiviral substances in Covid 19 by Molecular Docking: In Silico Study

Aims: This paper aimed to investigate the antiviral drugs against Sars-Cov-2 main protease (MPro) using in silico methods. Material(s) and Method(s): A search was made for antiviral drugs in the PubChem database and antiviral drugs such as Bictegravir, Emtricitabine, Entecavir, Lamivudine, Tenofovir, Favipiravir, Hydroxychloroquine, Lopinavir, Oseltamavir, Remdevisir, Ribavirin, Ritonavir were included in our study. The protein structure of Sars-Cov-2 Mpro (PDB ID: 6LU7) was taken from the Protein Data Bank (www.rcsb. Org) system and included in our study. Molecular docking was performed using AutoDock/Vina, a computational docking program. Protein-ligand interactions were performed with the AutoDock Vina program. 3D visualizations were made with the Discovery Studio 2020 program. N3 inhibitor method was used for our validation. Result(s): In the present study, bictegravir, remdevisir and lopinavir compounds in the Sars-Cov-2 Mpro structure showed higher binding affinity compared to the antiviral compounds N3 inhibitor, according to our molecular insertion results. However, the favipiravir, emtricitabine and lamuvidune compounds were detected very low binding affinity. Other antiviral compounds were found close binding affinity with the N3 inhibitor. Conclusion(s): Bictegravir, remdevisir and lopinavir drugs showed very good results compared to the N3 inhibitor. Therefore, they could be inhibitory in the Sars Cov-2 Mpro target.Copyright © 2023 Oner E et al.

Characteristics and Outcomes of Covid-19 in an Early-Treated Hiv Cohort in Thailand

Background: Emerging data indicate that people with HIV (PWH) are at risk of more severe outcomes from COVID-19. We described the clinical course and laboratory parameters pre-and post-COVID-19 in an early-treated HIV cohort in Thailand. Method(s): RV254 cohort participants were enrolled during Fiebig I-V acute HIV and initiated antiretroviral therapy (ART) within days. They underwent regular blood tests (CD4+ & CD8+ T-cell counts, HIV RNA), neuropsychiatric (NP) assessment (Color Trails 1 & 2, non-dominant hand Grooved Pegboard, Trails Making A), and mood questionnaires (Patient Health Questionnaire-9, Distress Thermometer) post-enrollment longitudinally. Their assessment outcomes pre-and post-COVID-19 were compared using Generalized Estimating Equations (GEE) with a normal distribution and identity link (CD4+, CD8+ T-cell counts, NP parameters) or binomial distribution with log link (HIV RNA), and autoregressive correlation structure. Result(s): Between 4/2021 and 9/2022, 295 participants on ART (98% male, median age 32 [IQR 28-37] were diagnosed with COVID-19. Of these, 16(5%), 38(13%) and 241(82%) were infected with alpha, delta and o variants, determined by the predominant strain circulating in Thailand at the time of infection;238(81%) received >=2 doses of COVID-19 vaccines prior to diagnosis;121(41%) received favipiravir. While 106 (36%) were managed in hospital or 'hospitel', including one intensive care unit admission, only 4(1.4%) received supplemental oxygen and none required mechanical ventilation (mean length of stay: 12 days). The participants were followed a median of 8 [IQR 5-15] weeks post-COVID. Comparing the outcomes pre-and post-COVID, plasma HIV suppression rate remained stable (98% vs. 96%, p=0.212). CD4+ (782 [IQR 708-856] vs. 823 [IQR 748-899], p=0.018) and CD8+ (622 [IQR 563-681] vs. 667 [IQR 605-728], p=0.023) T-cell counts were higher at follow-up after adjusting for age, sex, and duration between COVID-19 diagnosis and follow-up. The increasing trends of CD4+ and CD8+ T-cell were sustained on subsequent visits. Mood scores and NP performance (n=217) were stable at follow-up. Conclusion(s): In this cohort of young PWH on stable ART, we did not observe major clinical adverse events after COVID-19. Increases of CD4+ and CD8+ T-cell counts were observed while mood and NP parameters remained stable. More extensive NP assessment with incorporation of multimodal imaging outcomes and longer follow-up are needed to determine the long-term sequelae of COVID-19 in PWH.