ABSTRACT The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 remains a primary target for antiviral drug discovery. In this study, an integrated computational workflow—comprising molecular docking, triplicate 200 ns molecular dynamics (MD) simulations, Molecular Mechanics–Generalized Born Surface Area (MM/GBSA) binding free energy calculations, and free energy landscape (FEL) analysis—was employed to evaluate potential Mpro inhibitors. Five compounds exhibited higher predicted affinities than the crystallographic reference inhibitor 3W, with compounds 9g and 11e emerging as the most promising candidates. MD simulations demonstrated that both ligands enhanced the structural stability of Mpro, as evidenced by low root‐mean‐square deviation (RMSD) values, reduced root‐mean‐square fluctuation (RMSF) in key regions, and the maintenance of persistent hydrogen‐bond networks. Notably, compound 9g maintained stable interactions with the critical catalytic residue Glu166. MM/GBSA analysis yielded favorable binding free energies (Δ G bind ) of −38.84 kcal/mol for 9g and −32.52 kcal/mol for 11e, while FEL mapping confirmed their capacity to stabilize the protease in deep, energetically favorable conformational minima. Furthermore, the computational predictions correlated strongly with experimental IC50 data, validating the robustness of the applied workflow. These results provide molecular‐level insights into the potent inhibitory activity of 9g and 11e, identifying them as viable lead scaffolds for the development of optimized anti‐SARS‐CoV‐2 therapeutics.

The world has been devastated by the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 2019 to 2023 which necessitated stratifying patients into mild, moderate, severe, and critical categories based on clinical presentation, oxygen saturation, radiological findings, and systemic inflammatory response syndrome (SIRS). This study aimed to quantify lung involvement using high-resolution computed tomography (HRCT) and correlate it with clinical severity and laboratory parameters. This observational cross-sectional study was conducted at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from July to September 2020. A total of 90 RT-PCR-confirmed COVID-19 patients were enrolled from outpatient and inpatient departments on the basis of clinical and laboratory parameters in accordance with Interim Guidance, 27th May, 2020 on the Management of COVID-19 from WHO. The major CT findings and CT severity score were described by using internationally standard nomenclature defined by the Fleischner Society glossary and peer-reviewed literature on viral pneumonia. CT severity scores were calculated and statistically correlated with clinical severity and laboratory markers including SpO2, neutrophil and lymphocyte percentages, CRP, and D-dimer. A receiver operating characteristic (ROC) analysis was performed to determine a cutoff CT severity score for identifying severe cases. The mean CT severity score was 11.66, with severe cases showing significantly higher scores than non-severe cases (13 vs. 8.87). HRCT scores had a moderate negative correlation with SpO2 and lymphocyte percentage, and a moderate positive correlation with neutrophil percentage, CRP, and D-dimer. A CT severity score ≥ 8.5 was identified as the threshold for severe disease on ROC analysis. Age, sex, smoking status, and comorbidities had no relation with the severity of COVID-19. HRCT severity score had moderate negative correlation with disease severity of COVID-19. HRCT severity score is also found to have moderate positive correlation with total neutrophil percentage, CRP, and D-dimer; and moderate negative correlation with total lymphocyte percentage. No correlation was also found between increasing CT severity score with the presence of comorbidities. HRCT severity scoring showed a moderate correlation with clinical severity and laboratory markers in COVID-19, supporting its utility in triage and prognostication. Integrating HRCT scoring into clinical evaluations may enhance decision-making and patient management strategies.

Introduction: Coronavirus Disease 2019 (COVID-19) infection has been difficult to control despite advancements in medical science. Many short and long-term complications following COVID-19 infection are still being observed. The hypoxaemia episodes occurring in the first trimester of pregnant women and their potential role in causing congenital malformations in newborns remain unclear. Limited information is available regarding the effects of Severe Acute Respiratory Syndrome Coronavirus 2 (COVID-19) during the first trimester of pregnancy and its association with the risk of developing Major Congenital Malformations (MCMs). Aim: To compare the development of congenital malformations in pregnant women who tested SARS-CoV-2 positive and those who tested negative during the first trimester of pregnancy. Materials and Methods: A prospective cohort study was conducted in a small town in the Hooghly district of West Bengal between January 2021 and December 2021. Two nursing homes were selected for sample collection, with approximately 100 patients per centre. The study included 100 pregnant women in their first trimester who tested SARS-CoV-2 positive and another 100 pregnant women in their first trimester who tested negative. An unpaired t-test was performed to analyse the association between the development of MCMs in both groups. Results: The mean maternal age was comparable between the COVID-19-exposed group (24.6 years) and the nonexposed group (25.2 years). The proportions of primigravida and multigravida women were also similar in both groups (62% vs. 64% primigravida, respectively). The odds ratio for MCMs in the COVID-19-exposed group was 0.49, indicating a lower likelihood compared to the non-exposed group. The average Appearance (skin color), Pulse (heart rate), Grimace (reflex irritability/response), Activity (muscle tone), and Respiration (breathing effort) (APGAR) scores at 1 and 5 minutes were slightly higher in the exposed group (7.01 and 7.45) than in the non-exposed group (6.8 and 7.28), though the differences were not statistically significant (p=0.28 and p=0.50, respectively). Conclusion: The present study concludes that there is no evidence of increased risk of MCMs associated with firsttrimester maternal SARS-CoV-2 infection. Overall, the findings do not support any major teratogenic effects resulting from maternal COVID-19 infection in early pregnancy.

The evolution of Severe Acute Respiratory Syndrome Coronavirus 2 challenged the effectiveness of vaccines, while monoclonal antibodies (mAbs) were discontinued due to emergent resistance. This study evaluated the safety and explored the preliminary efficacy of COR-101, a novel mAb with a silenced Fc region designed to minimize antibody-dependent enhancement in hospitalized patients with moderate-to-severe disease. Thirty-three participants were enrolled across Germany and Ukraine in a randomized, double-blind, placebo-controlled Phase Ib/II trial. Patients received either a single dose of COR-101, or placebo, as add-on therapy to the standard of care. COR-101 was well tolerated, with no treatment-related severe adverse events (AEs), grade ≥3 AEs, or acute infusion reactions. Four unrelated severe AEs were observed, and 2 patients died due to coronavirus disease 2019. COR-101 showed dose-proportional pharmacokinetics, long half-life, and serum concentrations above IC50. Patients were treated in different dose groups, and in exploratory analysis, viral clearance was observed at day 28 in 80%, 55.6%, 16.7%, and 42.9% of patients in the 4.0, 10.0, 25.0 mg/kg, and placebo groups, respectively. The predominant virus variant changed from alpha to delta and omicron, resulting in reduced in vitro neutralization, potentially explaining the observed reduced efficacy. COR-101 demonstrated a favorable safety profile, but exploratory data showed limited efficacy against omicron, highlighting the tolerability of Fc-silenced mAbs and the need for adaptive therapeutic strategies against rapidly evolving viral pathogens (ClinicalTrials.gov identifier: NCT04674566).

Severe Acute Respiratory Syndrome Coronavirus 2 was declared a public health emergency of international concern in March 2020. This virus evolved into different genetic variants that circulated worldwide. Local genomic surveillance was crucial for the pandemic response. The objective of the research consisted in characterize the genomic surveillance of SARS-CoV-2 from confirmed cases at the Villa Clara LBM (Base Laboratory) during the study period. A cross-sectional descriptive study was conducted from December 2020 to May 2023. The study utilized 106 nasopharyngeal swab samples from patients confirmed by RT-PCR at the Villa Clara LBM, which were sent for nucleotide sequencing to the LNR-IVR-IPK (National Reference Laboratory-Insect Vector Department at the Pedro Kourí Institute). Patients infected with the Delta variant presented severe forms of the disease in 43.75% of cases. The Delta variant had the lowest median cycle threshold value (18.50). 100% of patients with the Delta variant had the mutations found in subgroup 3 (D614G, L452R, P681H, T478K). In the phylogenetic tree, the branch grouping the Omicron variant showed high genetic diversity. The use of genomic surveillance during the COVID-19 pandemic was essential for understanding the clinical-epidemiological dynamics linked to each circulating SARS-CoV-2 variant in Villa Clara province.

Severe acute respiratory syndrome coronavirus 2 infects host cells through binding of the spike protein receptor-binding domain (RBD) to the human angiotensin-converting enzyme 2 receptor. In this study, the antiviral activity of 14 catechin derivatives was evaluated using a pseudovirus assay that emulates spike-mediated cell fusion. Of these, gallocatechin gallate, epigallocatechin gallate, epigallocatechin 3-(3″-O-methyl) gallate, and epigallocatechin exhibit strong inhibitory effects on infection. A structural comparison of the compounds revealed that catechins with a pyrogallol-type B-ring configuration exhibited greater inhibitory effects than their catechol-type counterparts. Docking simulations demonstrated that the hydroxyl group at the 5-position of the B-ring forms a hydrogen bond with Gln493 on the spike RBD, thereby facilitating additional stabilizing interactions with adjacent residues, such as Tyr453. Although catechin bioavailability is low, the results of this study suggest that regular consumption or gargling may offer localized antiviral activity at mucosal surfaces, such as those found in the oral or nasal cavity, because the catechin concentrations used in the cell assays are similar to those observed in green tea (100µM). This study underscores the potential of pyrogallol-type catechins to act as antiviral agents.

BACKGROUNDDue to immunosuppression (IS) use, patients with autoimmune hepatitis (AIH) may be at high risk for poor coronavirus disease 2019 (COVID-19) outcomes.AIMTo investigate the associations between IS type and COVID-19 severity in AIH patients using the National Clinical Cohort Collaborative (N3C) COVID enclave.METHODSWe identified all AIH patients with COVID-19 in the N3C COVID enclave. We used adjusted logistic regressions to determine associations between IS type and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We used Cox models to determine associations between IS type and all-cause mortality in the subset of AIH patients infected with SARS-CoV-2.RESULTSOf 15187 AIH patients, 5106 (33%) had IS exposure, and 1604 (11%) tested positive for SARS-CoV-2 during the study period from March 2020 through March 2025. There was an association with prednisone [odds ratio (OR): 0.81, 95%CI: 0.65-0.99, P = 0.04] exposure and SARS-CoV-2 test positivity. For interactions between different IS combinations and SARS-CoV-2 test positivity in the overall cohort, budesonide and azathioprine (OR: 1.88, 95%CI: 1.02-3.44, P = 0.04) and prednisone and tacrolimus interactions (OR: 1.99, 95%CI: 1.14-3.53, P = 0.02) showed significant associations. Within the subgroup finding of patients with full model for end stage liver disease data, budesonide and azathioprine interaction (OR: 4.44, 95%CI: 1.29-16.72, P = 0.02) also had a significant association. In our adjusted Cox regressions and corresponding subgroup analysis, we found no specific IS type that was statistically significant in association with all-cause mortality.CONCLUSIONPrednisone exposure was negatively associated, and statistically significant IS interactions were positively associated with testing positive for SARS-CoV-2. Further work involves determining the impact of vaccinations and advances in COVID-19 treatment on outcomes in this population.

The current study aimed to assess the levels of total IgG antibodies against the spike (S) and nucleocapsid (N) proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as the neutralizing antibodies (nAbs) in a population of Crete, Greece. In total, 1,061 participants with 2,081 follow-up measurements during May-December 2022, from eight different primary healthcare facilities, were categorized into four groups, based on vaccination and illness status. Blood samples were collected and processed to measure anti-S, anti-N and neutralizing antibodies. Based on specific cutoff values and using non-parametric methods, antibody levels were compared between different categories or disease/vaccination of SARS-CoV-2. The proportion of participants who had been infected was higher among the unvaccinated. Additionally, an increase in the number of vaccine doses administered resulted in a noteworthy reduction in the frequency of illness, with proportions decreasing from 69.2% among those who were not vaccinated or 83.1% among those vaccinated 1-2 times to 21.6% among those vaccinated 4+ times (p<0.001). Also, participants who were vaccinated and contracted the infection presented higher levels of anti-S antibodies compared to those who were unvaccinated and did not develop symptoms (471.10 vs. 83.27, p<0.001). This population-based seroepidemiological study underscores the synergistic impact of vaccination and natural infection in sustaining elevated antibody levels during the Omicron period. The findings emphasize the importance of continuous immunological surveillance within primary healthcare settings to identify individuals at risk of declining immunization and to inform evidence-based booster vaccination strategies, thereby enhancing preparedness and resilience against future pandemic responses.

This study presents findings from a systematic review of Coronavirus Disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) which has posed great threat to the world, causing devastating effects, especially, on health, social life and economy. Data show that immunocompetent patients have been affected with COVID-19, however, much impact have rather, been reported on the immunocompromised patients as they have elevated risk of severe outcomes of morbidity, resulting in increased hospitalization and death from SAR-CoV-2 infection. This contributed to increased number of cases and death worldwide. The review gives an overview of the diagnoses, immmunocompromised conditions, impacts and clinical management strategies of immunocompromised patients. It adopts a systematic review as a design to collate and analyze the impacts of COVID-19 on immunocompromised patients from literature covering 2019 and 2025. Results revealed that complement protein deficiencies, defect in innate immunity, antibody deficiencies, T and B lymphocytes deficiencies, autoinflammatory disorders among others have been identified as the cause of Primary Immmunocompromised Disorders while major medical conditions and treatments such as cancer, HIV, solid-organ transplantation and immunosuppressive drugs caused Secondary Immmunocompromised Disorders. Clinical therapies identified were the use of pre-exposure prophylaxis, monoclonal antibodies, lymphocyte infusion, antiviral drugs, antiretroviral therapy and immunoglobulin maintenance. However, Immunocompromised conditions varies from persons to persons, therefore, specific clinical therapeutic measures should be used by health care providers depending on the type of immunocompromised conditions for proper management of COVID-19 infection.Keywords: COVID-19; immunocompromised patients; immunocompetent patients; Primary Immunocompromised Disorders (PIDs); Secondary Immunocompromised Disorders (SIDs)

Idiopathic pulmonary fibrosis (IPF) is a serious progressive complication of the respiratory system, which is profoundly associated with persistent extracellular matrix (ECM) deposition, fibrosis, and disrupted tissue regeneration. Emerging evidence shows that epithelial-mesenchymal transition (EMT) acts as a key factor in the pathogenesis of this idiopathic interstitial lung disease by connecting long-lasting epithelial damage to fibroblast accumulation and fibrotic processes. Viral pathogens, particularly emerging and re-emerging viruses, such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Influenza Virus, and Dengue Virus (DENV) and also those with oncogenic potential such as Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), and Hepatitis C Virus (HCV), have been demonstrated to be significantly associated with impaired epithelial signalling, persistent inflammation, and EMT induction. This underscores the presence of potential mechanistic overlap between viral infections and fibrotic complications of the respiratory system. On the other hand, investigations have also suggested the capacity of Traditional Chinese Medicine (TCM) agents to modulate various EMT-linked pathways, which are simultaneously involved in both viral infections and IPF development. These common signalling pathways include TGF-β, Wnt/β-catenin, PI3K/AKT, and NF-κB signalling, acting as potential therapeutic targets against fibrotic complications such as IPF. The present review aims to comprehensively describe current evidence on the dynamic cross-talk between viral pathogens, particularly SARS-CoV-2, Influenza Virus, and DENV, EMT, and lung fibrosis. Additionally, it critically discusses how TCM-derived bioactive agents can interfere with these interconnected processes. This review elucidates the mechanistic basis and therapeutic potential of TCM compounds in lung fibrosis, considering the wider context of virus-related EMT dysregulation.

Nasopharyngeal swabs (NASO) cause discomfort for patients, which can discourage them from getting tested for COVID-19 and limit case detection. It is therefore necessary to consider an alternative, more comfortable swab. Evaluated the concordance between nasopharyngeal and oropharyngeal sampling for COVID-19 diagnosis in the Cameroonian context. This study was carried out at "Chantal Biya" International Reference Centre for Research on HIV/AIDS Prevention and Management (CIRCB) in Yaoundé, Cameroon. A comparative study was conducted in April 2021 among consenting participants tested for COVID-19 at "Chantal Biya" International Reference Centre for Research on HIV/AIDS Prevention and Management (CIRCB) in Yaoundé, Cameroon. Sampling began with nasopharyngeal swabs, followed by oropharyngeal swabs, all taken by the same technician, and analysis was carried out using polymerase chain reaction (PCR) tests on the Abbott platform. Statistical analyses were performed using GraphPad version 6.0; p < 0.05 was considered statistically significant. A total of 154 participants were enrolled (59.7% male, median age 38 years, interquartile range [IQR]: 30-49). Following PCR testing, the overall COVID-19 positivity rate was 36.36% (56/154), with 34.41% (n = 53/154) in nasopharyngeal versus 16.23% (n = 25/154) in oropharyngeal samples, p < 0.0002. The overall concordance rate was 78% (n = 120/154), with 39.28% positive concordance and 74.24% negative concordance (kappa = 0.441 [0.289-0.513]). According to severe acute respiratory syndrome coronavirus 2 viral load, the positive concordance was improved with high viral load (cycle threshold [CT]: ≤ 25): 61% (n = 11/18) versus 31% (n = 11/35) with low viral load (CT > 25), p = 0.037; odds ratio (OR) = 3.43. According to gender, the positive concordance was higher in men, 55% (n = 16/29), versus 25% (n = 6/24) in women, p = 0.021; OR = 0.27. Using nasopharyngeal swab as the gold standard, oropharyngeal swab had a sensitivity of 41.50% (n = 22/53), specificity 97.02% (n = 98/101), positive predictive value (PPV) 88% (n = 22/25) and negative predictive value (NPV) 76% (n = 98/129). Our evidence suggests a superiority effect of nasopharyngeal in detecting cases of COVID-19. However, the overall high PPV of oropharyngeal swab, and its improved performance with high viral load. Therefore, in case of counter-indication to nasopharyngeal swabbing, oropharyngeal can be an acceptable alternative.

Erythema multiforme (EM) is typically self-limiting, however severe EM major may cause significant morbidity and lacks evidence-based therapeutic guidelines. Intravenous immunoglobulin (IVIg) has primarily been used in recurrent EM. This study evaluates IVIg use in severe first-episode or steroid-recalcitrant EM major. A retrospective analysis reviewed six EM major patients treated with IVIg at a tertiary Australian hospital. IVIg was administered in eight instances. Disease triggers included Mycoplasma pneumoniae in three admissions, unknown aetiology in three admissions, rhinovirus/influenza A in one admission, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus) in one admission. Two patients developed recurrent EM. All patients received systemic corticosteroids. All patients received IVIg within four days of admission, demonstrating complete response to therapy with a mean improvement time of 4.75 days. IVIg was well-tolerated and demonstrated efficacy in severe or corticosteroid-refractory EM major. Further studies are required to validate its efficacy.

Computational blind challenges offer critical, unbiased opportunities to assess and accelerate scientific progress, as demonstrated by a breadth of breakthroughs over the past decade. We report the outcomes and key insights from an open science community blind challenge focused on computational methods in drug discovery, using lead optimization data from the AI-driven Structure-enabled Antiviral Platform Discovery Consortium's pan-coronavirus antiviral discovery program, in partnership with Polaris and the OpenADMET project. This collaborative initiative invited global participants from both academia and industry to develop and apply computational methods to predict the biochemical potency and crystallographic ligand poses of small molecules against key coronavirus targets, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) main protease (Mpro), as well as multiple ADMET assay end points, using previously undisclosed comprehensive experimental drug discovery data sets as benchmarks. By evaluating submissions across multiple tasks and compounds, we established performance leaderboards and conducted meta-analyses to assess methodological strengths, common pitfalls, and areas for improvement. This analysis provides a foundation for best practices in real-world machine learning evaluation, grounded in community-driven benchmarking. We also highlight how next-generation platforms, such as Polaris, enable rigorous challenge design, embedded evaluation frameworks, and broad community engagement. This paper reports the collective findings of the challenge, offering a high-level overview of the data, evaluation infrastructure, and top-performing strategies. We further provide context and support for the accompanying papers authored by the challenge participants in this special issue, which explore individual approaches in greater depth. Together, these contributions aim to advance reproducible, trustworthy, and high-impact computational methods in drug discovery, and to explore best practices and pitfalls in future blind challenge design and execution, including planned initiatives for the OpenADMET project.

Respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in infants differ substantially in their clinical presentations and outcomes. RSV is the leading cause of severe lower respiratory tract infection in infants, whereas SARS-CoV-2 infections are typically milder and do not necessarily involve the lower respiratory tract. To uncover immune mechanisms associated with these differences, we analyzed blood samples from infants (median age, 2.3 months) infected with RSV (n=19) or SARS-CoV-2 (n=30), as well as healthy control infants (n=17), using cytokine profiling, single-cell transcriptomics, and epigenomics. Both viruses induced comparable interferon-stimulated gene signatures but displayed disease-specific signatures in the individual cell types analyzed. Specifically, RSV was associated with increased CD4+ terminal effector memory T cell and memory regulatory T cell frequencies in the peripheral blood. Infants with severe RSV had reduced natural killer cell frequencies in the blood, lower IFNG expression in CD56dim natural killer cells, and diminished chromatin accessibility at T-BET and EOMES binding sites in CD56dim and CD56bright natural killer cells. In contrast, infants infected with SARS-CoV-2 showed heightened proinflammatory responses in the blood, including higher nuclear factor κB pathway activity and serum tumor necrosis factor concentrations. These results highlight the distinct nature of infant immune responses to RSV and SARS-CoV-2 infections, offering insights that may help explain differences in the clinic and guide therapies.

Therapeutic Approaches to Treat SARS-CoV-2.

Background:Severe coronavirus disease 2019 (COVID-19) is characterized by a hyperinflammatory state associated with an exacerbated inflammatory activation of monocytes and macrophages in the respiratory tract. Metformin has been identified as a potent monocyte inflammatory suppressor, and it has been demonstrated to attenuate inflammation in COVID-19. The mechanisms underlying metformin’s anti-inflammatory effects are, however, unclear. We thus sought to investigate metformin’s main interactions and their respective isolated effects in modulating monocyte inflammatory response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) stimulation.Methods:Classical human monocytes were isolated from healthy 18 to 40-year-old individuals and stimulated in vitro with recombinant spike protein subunit 1 (rS1) to assess glycolytic and oxidative metabolic responses by Seahorse extracellular flux analysis and inflammatory gene expression by quantitative polymerase chain reaction. Stimulated monocytes were either pretreated with metformin, rotenone, S1QEL, or A769662.Results:Monocytes stimulated in vitro with rS1 showed an increased glycolytic response associated with production of pro-inflammatory cytokines. Metformin pretreatment reduced glycolytic activation while partially suppressing inflammation. Rotenone-dependent mitochondrial complex I inhibition was not able to replicate the same effect, and neither was complex I-specific reactive oxygen species scavenging. Conversely, A769662-induced AMP-activated protein kinase (AMPK) activation led to suppressed glycolytic inflammatory response and cytokine expression pattern similar to metformin, thus suggesting AMPK modulation as a possible central component for metformin’s mode of action upon S1 stimulation.Conclusions:In summary, further investigation into the interactions underlying AMPK activity on monocytes in the context of SARS-CoV-2 may provide a better elucidation of metformin’s anti-inflammatory effect.

The coronavirus disease 2019 (COVID-19) pandemic has prompted extensive research into therapeutic options, including traditional ayurvedic medicine. This study aims to investigate the safety and efficacy of herbal formulation through in vitro, in silico, and clinical trials. An in vitro antiviral assay was performed using a plaque assay to evaluate the percentage of virus inhibition. In silico analysis utilized AutoDock 4.2.6 to assess binding affinities of 95 active ingredients in the formulation against key severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets, including Papain-like protease, RNA-dependent RNA polymerase, nucleocapside proteins, non-structural protein-1, and open reading frame 6. The first trial was an open-label study involving 60 subjects, where 30 received the test formulation alongside standard treatment, while the other 30 received standard treatment alone. This was followed by a double-blind trial with 60 participants randomly assigned to receive either the test formulation or a placebo along with standard treatment. The in vitro assay indicated that the herbal formulation reduced viral load by 94.51% at 48 hpi. In silico analysis revealed that phyto-compounds demonstrated stronger binding energies with target proteins than remdesivir. Clinical trials showed significant reductions in disease progression and symptom alleviation; an open-label trial recorded a recovery rate of 96.7%, while a double-blind trial reported a recovery rate of 93.3% within 7 days and 100% recovery rate recorded within 10 days in both trials. Notably, the formulation reduced the inflammatory markers and enhanced the immune responses. The herbal formulation showed potent antiviral activity in vitro and strong molecular binding with key SARS-CoV-2 proteins in silico. Clinical data demonstrated accelerated recovery and improved immune modulation, highlighting the formulation's therapeutic potential as a complementary option for COVID-19 management. The herbal formulation demonstrated its potential as an effective adjuvant therapy for COVID-19, supported by comprehensive preclinical, computational, and clinical evidence. This study underscores the integration of novel herbal formulation with contemporary scientific methodologies to address global health challenges effectively. Clinical trial numbers: Clinical Trials Registry of India (CTRI/2020/05/025340; CTRI/2021/06/034132).

The coronavirus disease 2019 (COVID-19) pandemic has stimulated extensive endeavors toward the development of therapeutic interventions targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human proteins for viral infection control, encompassing numerous potential drugs and thousands of patients participating in clinical trials. These concerted efforts have resulted in significant advancements in antiviral drug discovery and development. In this review, we present a comprehensive timeline detailing the development of antiviral drugs, tracing the progression from early viral inhibitors to modern broad-spectrum antiviral agents. We also outline the current status of advancements in antiviral drug discovery, encompassing target-based strategies, innovative mechanism-based approaches, and pharmacokinetic optimization. Furthermore, we discuss the challenges and future prospects gained from COVID-19 and other infectious diseases, covering knowledge of artificial intelligence strategies, the utilization of medicinal chemistry tools, and advancements in nanotechnology applications. The application of artificial intelligence in drug discovery is increasingly prevalent, particularly in the areas of protein structure prediction, drug target identification, and bioactivity forecasting. Nanotechnology has played a crucial role in the delivery of antiviral drugs and the development of vaccines, exemplified by the use of lipid nanoparticles in mRNA vaccines. Additionally, we highlight potential future directions for drug discovery, such as targeting membraneless organelles (liquid‒liquid phase separation).

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can cause persistent, multisystem complications collectively termed long COVID. Cardiovascular sequelae are among the most clinically significant yet remain incompletely characterized. This review aimed to synthesize current evidence on objective cardiovascular outcomes in long COVID and explore underlying mechanisms. Methods: A systematic review was conducted using PubMed, Scopus, and Web of Science for studies published between January 2020 and March 2024. Search terms included “COVID-19,” “long COVID,” “post-acute sequelae,” “cardiovascular,” “echocardiography,” “biomarkers,” and “imaging.” Only studies reporting at least one cardiovascular outcome, defined as either objectively measured parameters (e.g., echocardiography, cardiac biomarkers, ECG findings, or vascular function indices) or clinically relevant cardiovascular symptoms during follow-up, were included. From 412 identified records, ten recent, high-quality studies with a primary cardiovascular focus were selected. This systematic review was conducted in accordance with the PRISMA 2020 guidelines. Results: Long COVID is associated with subclinical myocardial dysfunction, arrhythmias, endothelial injury, vascular stiffness, and a prothrombotic state. Reported findings included reduced left ventricular ejection fraction, impaired global longitudinal strain, increased arterial stiffness, elevated cardiac biomarkers, new-onset hypertension, and persistent ECG changes, even in non-hospitalized patients without prior cardiovascular disease. Proposed mechanisms include myocardial inflammation, endothelial dysfunction, renin–angiotensin–aldosterone system dysregulation, autonomic imbalance, and chronic inflammation. Secondary bacterial and fungal infections were noted in critically ill survivors but did not fully explain the breadth or persistence of symptoms. Conclusions: Long COVID is a heterogeneous entity with substantial cardiovascular implications across all levels of acute disease severity. Early detection through longitudinal monitoring, standardized definitions, and multidisciplinary care is essential to reduce long-term cardiovascular risk.

Viruses suddenly emerging from obscurity or anonymity affect our quality of life and increase incidence rate and mortality. A typical example is the global coronavirus disease 2019 (COVID-19) pandemic. Although severe acute respiratory syndrome coronavirus 2, known as the pathogen of COVID-19 has been significantly eliminated, its monitoring is still crucial, as the infectious disease may break out again. Therefore, it is necessary to develop simple and effective tools for monitoring COVID-19 and other diseases. Here, we summarize the progress of machine-learning-based biosensors in the monitoring and management of COVID-19. This article mainly includes three sections: machine learning algorithms, machine-learning-assisted biosensors, and challenges and future perspectives. We believe that this work is valuable for developing artificial-intelligence-based innovative analytical devices for healthcare monitoring and management of COVID-19 and other infectious diseases.