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The process of viral entry into host cells is crucial for the establishment of infection and the determination of viral pathogenicity. A comprehensive understanding of entry pathways is fundamental for the development of novel therapeutic strategies. Standard techniques for investigating viral entry include confocal microscopy and flow cytometry, both of which provide complementary qualitative and quantitative data. Imaging flow cytometry, which integrates the advantages of both methodologies, offers significant potential in virological studies. In this investigation, we employed imaging flow cytometry coupled with immunostaining to monitor the entry of equine arteritis virus EAV into Vero cells via the endosomal trafficking route. Analysis provided an insight into the early infection dynamics across thousands of cells, revealing statistically significant alterations in internalization and uncoating process. Moreover, we evaluated the effectiveness of two inhibitors targeting cellular factors involved in facilitating viral entry: ammonium chloride, which disrupts endocytosis, and camostat mesylate, which inhibits the activity of serine proteases. The results demonstrated a clear distinction between effective and ineffective inhibitors. This study highlighted the potential of imaging flow cytometry to advance the study of viral entry and the evaluation of antiviral agents. [ABSTRACT FROM AUTHOR]

[Display omitted] • COVID-19 is an emerging viral pandemic causing public health threats globally. • COVID-19 induces neurological, nephrological, gastrointestinal, cardiovascular, immune, and hepatic abnormalities. • Antibodies and drugs with potential efficacy against COVID-19 with their mechanism of action, synthetic protocols, and clinical data are discussed. • The antiviral effect and synthetic schemes of antiviral drugs are useful for finding leads to reduce the COVID-19 viral load. COVID-19 is an emerging viral pandemic caused by SARS-CoV-2, which is the causative agent of unprecedented disease-causing public health threats globally. Worldwide, this outbreak is wreaking havoc due to failure in risk assessment regarding the urgency of the pandemic. As per the reports, many secondary complications which include neurological, nephrological, gastrointestinal, cardiovascular, immune, and hepatic abnormalities, are linked with COVID −19 infection which is associated with prominent respiratory disorders including pneumonia. Hindering the initial binding of the virus with Angiotensin-converting enzyme 2 (ACE2) through the spike protein is one potential boulevard of monoclonal antibodies. Although some drug regimens and vaccines have shown safety in trials, none have been entirely successful yet. This review highlights, some of the potential antibodies (tocilizumab, Sarilumab, Avdoralimab, Lenzilumab, Interferon (alfa /beta /gamma)) screened against SARS-CoV-2 and the most promising drugs (Favipiravir, Hydroxychloroquine, Niclosamide, Ribavirin, Baricitinib, Remdesivir, Arbidol Losartan, Ritonavir, Lopinavir, Baloxavir, Nitazoxanide, Camostat) in various stages of development with their synthetic protocol and their clinical projects are discussed to counter COVID −19. [ABSTRACT FROM AUTHOR]

The human transmembrane protease, serine 2 (TMPRSS2), essential for SARS-CoV-2 entry, is a key antiviral target. Here, we computationally profiled the TMPRSS2-binding affinities of 15 antiviral compounds. Molecular dynamics (MD) simulations for the docked complexes revealed that three compounds exited the substrate-binding cavity (SBC), suggesting noncompetitive inhibition. Of the remaining compounds, five charged ones exhibited reduced binding stability due to competing electrostatic interactions and increased solvent exposure, while seven neutral compounds showed stronger binding affinity driven by van der Waals (vdW) interactions compensating for unfavorable electrostatic effects (including electrostatic interactions and desolvation penalties). Positive and negative hotspot residues were identified as uncharged and charged, respectively, both lining the SBC. Despite forming diverse interactions with compounds, the burial of positive hotspots led to strong vdW interactions that overcompensated for unfavorable electrostatic effects, whereas negative hotspots incurred high desolvation penalties, negating any favorable contributions. Charged residues at the SBC's outer rim can reduce binding affinity significantly when forming hydrogen bonds or salt bridges. These findings underscore the importance of enhancing vdW interactions with uncharged residues and minimizing the unfavorable electrostatic effects of charged residues, providing valuable insights for designing effective TMPRSS2 inhibitors. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic, driven by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has evolved into an unprecedented global health crisis, encompassing zoonotic origins, a shift in human-to-human transmission dynamics and global dissemination. The present review navigates through the complexities of COVID-19. Beyond mild respiratory symptoms, the clinical spectrum includes severe conditions, such as multi-organ failure, pneumonia and acute respiratory distress syndrome. The critical evaluation of COVID-19 diagnostic techniques, including PCR, antigen tests and serological assays, emphasizes their pivotal role in disease detection, management, contact tracing and containment. As regards the therapeutic domain, the present review discusses treatments, such as antivirals, immunomodulatory therapies and repurposed pharmaceuticals, with an emphasis on vaccine development for epidemic containment and herd immunity. Despite progress being made, global healthcare systems face formidable challenges, including equitable vaccine distribution, combatting disinformation, viral mutation management and strategic planning for future outbreaks. A comparative analysis of SARS highlights the need to distinguish between these diseases for effective epidemic management. The present review aimed to provide profound insight into the diverse nature of COVID-19, fostering a more in-depth understanding, and guiding future research and public health initiatives. [ABSTRACT FROM AUTHOR]