Viruses

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26 pages, 7300 KiB

Open AccessArticle

Computational Evidence for Bisartan Arginine Blockers as Next-Generation Pan-Antiviral Therapeutics Targeting SARS-CoV-2, Influenza, and Respiratory Syncytial Viruses

by Harry Ridgway, Vasso Apostolopoulos, Graham J. Moore, Laura Kate Gadanec, Anthony Zulli, Jordan Swiderski, Sotirios Tsiodras, Konstantinos Kelaidonis, Christos T. Chasapis and John M. Matsoukas

Viruses 2024, 16(11), 1776; https://doi.org/10.3390/v16111776 - 14 Nov 2024

Viewed by 950

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, and respiratory syncytial virus (RSV) are significant global health threats. The need for low-cost, easily synthesized oral drugs for rapid deployment during outbreaks is crucial. Broad-spectrum therapeutics, or pan-antivirals, are designed to target multiple viral [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, and respiratory syncytial virus (RSV) are significant global health threats. The need for low-cost, easily synthesized oral drugs for rapid deployment during outbreaks is crucial. Broad-spectrum therapeutics, or pan-antivirals, are designed to target multiple viral pathogens simultaneously by focusing on shared molecular features, such as common metal cofactors or conserved residues in viral catalytic domains. This study introduces a new generation of potent sartans, known as bisartans, engineered in our laboratories with negative charges from carboxylate or tetrazolate groups. These anionic tetrazoles interact strongly with cationic arginine residues or metal cations (e.g., Zn²⁺) within viral and host target sites, including the SARS-CoV-2 ACE2 receptor, influenza H1N1 neuraminidases, and the RSV fusion protein. Using virtual ligand docking and molecular dynamics, we investigated how bisartans and their analogs bind to these viral receptors, potentially blocking infection through a pan-antiviral mechanism. Bisartan, ACC519TT, demonstrated stable and high-affinity docking to key catalytic domains of the SARS-CoV-2 NSP3, H1N1 neuraminidase, and RSV fusion protein, outperforming FDA-approved drugs like Paxlovid and oseltamivir. It also showed strong binding to the arginine-rich furin cleavage sites S1/S2 and S2′, suggesting interference with SARS-CoV-2’s spike protein cleavage. The results highlight the potential of tetrazole-based bisartans as promising candidates for developing broad-spectrum antiviral therapies. Full article

(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 3rd Edition)

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15 pages, 2518 KiB

Open AccessArticle

Molecular Characterization and Genomic Surveillance of SARS-CoV-2 Lineages in Central India

by Purna Dwivedi, Mukul Sharma, Afzal Ansari, Arup Ghosh, Subasa C. Bishwal, Suman Kumar Ray, Manish Katiyar, Subbiah Kombiah, Ashok Kumar, Lalit Sahare, Mahendra Ukey, Pradip V. Barde, Aparup Das and Pushpendra Singh

Viruses 2024, 16(10), 1608; https://doi.org/10.3390/v16101608 - 14 Oct 2024

Viewed by 822

Abstract

Since the first reported case of COVID-19 in December 2019, several SARS-CoV-2 variants have evolved, and some of them have shown higher transmissibility, becoming the prevalent strains. Genomic epidemiological investigations into strains from different time points, including the early stages of the pandemic, [...] Read more.

Since the first reported case of COVID-19 in December 2019, several SARS-CoV-2 variants have evolved, and some of them have shown higher transmissibility, becoming the prevalent strains. Genomic epidemiological investigations into strains from different time points, including the early stages of the pandemic, are very crucial for understanding the evolution and transmission patterns. Using whole-genome sequences, our study describes the early landscape of SARS-CoV-2 variants in central India retrospectively (including the first known occurrence of SARS-CoV-2 in Madhya Pradesh). We performed amplicon-based whole-genome sequencing of randomly selected SARS-CoV-2 isolates (n = 38) collected between 2020 and 2022 at state level VRDL, ICMR-NIRTH, Jabalpur, from 11899 RT-qPCR-positive samples. We observed the presence of five lineages, namely B.1, B.1.1, B.1.36.8, B.1.195, and B.6, in 19 genomes from the first wave cases and variants of concern (VOCs) lineages, i.e., B.1.617.2 (Delta) and BA.2.10 (Omicron) in the second wave cases. There was a shift in mutational pattern in the spike protein coding region of SRAS-CoV-2 strains from the second wave in contrast to the first wave. In the first wave of infections, we observed variations in the ORF1Ab region, and with the emergence of Delta lineages, the D614G mutation associated with an increase in infectivity became a prominent change. We have identified five immune escape variants in the S gene, P681R, P681H, L452R, Q57H, and N501Y, in the isolates collected during the second wave. Furthermore, these genomes were compared with 2160 complete genome sequences reported from central India that encompass 109 different SARS-CoV-2 lineages. Among them, VOC lineages Delta (28.93%) and Omicron (56.11%) were circulating predominantly in this region. This study provides useful insights into the genetic diversity of SARS-CoV-2 strains over the initial course of the COVID-19 pandemic in central India. Full article

(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 3rd Edition)

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12 pages, 779 KiB

Open AccessArticle

Wastewater Surveillance of SARS-CoV-2: A Comparison of Two Concentration Methods

by Christina Diamanti, Lambros Nousis, Petros Bozidis, Michalis Koureas, Maria Kyritsi, George Markozannes, Nikolaos Simantiris, Eirini Panteli, Anastasia Koutsolioutsou, Konstantinos Tsilidis, Christos Hadjichristodoulou, Alexandra Koutsotoli, Eirini Christaki, Dimitrios Alivertis, Aristides Bartzokas, Konstantina Gartzonika, Chrysostomos Dovas and Evangelia Ntzani

Viruses 2024, 16(9), 1398; https://doi.org/10.3390/v16091398 - 31 Aug 2024

Viewed by 1003

Abstract

Wastewater surveillance is crucial for the epidemiological monitoring of SARS-CoV-2. Various concentration techniques, such as skimmed milk flocculation (SMF) and polyethylene glycol (PEG) precipitation, are employed to isolate the virus effectively. This study aims to compare these two methods and determine the one [...] Read more.

Wastewater surveillance is crucial for the epidemiological monitoring of SARS-CoV-2. Various concentration techniques, such as skimmed milk flocculation (SMF) and polyethylene glycol (PEG) precipitation, are employed to isolate the virus effectively. This study aims to compare these two methods and determine the one with the superior recovery rates. From February to December 2021, 24-h wastewater samples were collected from the Ioannina Wastewater Treatment Plant’s inlet and processed using both techniques. Subsequent viral genome isolation and a real-time RT-qPCR detection of SARS-CoV-2 were performed. The quantitative analysis demonstrated a higher detection sensitivity with a PEG-based concentration than SMF. Moreover, when the samples were positive by both methods, PEG consistently yielded higher viral loads. These findings underscore the need for further research into concentration methodologies and the development of precise protocols to enhance epidemiological surveillance through wastewater analysis. Full article

(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 3rd Edition)

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10 pages, 1542 KiB

Open AccessCommunication

Suspected Human-to-Cat Spillover of SARS-CoV-2 Omicron Variant in South Korea

by Ju-Hee Yang, Yeonsu Oh, Sung-Hyun Moon, Gun-Hee Lee, Jae-Young Kim, Yeon-Kyung Shin, Dongseob Tark and Ho-Seong Cho

Viruses 2024, 16(7), 1113; https://doi.org/10.3390/v16071113 - 11 Jul 2024

Viewed by 925

Abstract

This retrospective study reports the isolation and characterization of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) from a household cat in South Korea. The cat, which was presented with respiratory symptoms, was identified during a retrospective analysis of samples collected between April 2021 [...] Read more.

This retrospective study reports the isolation and characterization of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) from a household cat in South Korea. The cat, which was presented with respiratory symptoms, was identified during a retrospective analysis of samples collected between April 2021 and March 2022. Genomic sequencing revealed that the isolated virus belonged to the Omicron variant (BA.1), coinciding with its global emergence in early 2022. This case study provides evidence for the potential of direct human-to-cat transmission of the Omicron variant in South Korea during its period of widespread circulation. Our findings underscore the importance of continuous monitoring of SARS-CoV-2 in both human and animal populations to track viral evolution and potential spillover events. Full article

(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 3rd Edition)

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12 pages, 5072 KiB

Open AccessArticle

Mutations in the Receptor Binding Domain of Severe Acute Respiratory Coronavirus-2 Omicron Variant Spike Protein Significantly Stabilizes Its Conformation

by Michael H. Peters

Viruses 2024, 16(6), 912; https://doi.org/10.3390/v16060912 - 4 Jun 2024

Cited by 1 | Viewed by 834

Abstract

The Omicron variant and its sub-lineages are the only current circulating SARS-CoV-2 viruses worldwide. In this study, the conformational stability of the isolated Receptor Binding Domain (RBD) of Omicron’s spike protein is examined in detail. The parent Omicron lineage has over ten mutations [...] Read more.

The Omicron variant and its sub-lineages are the only current circulating SARS-CoV-2 viruses worldwide. In this study, the conformational stability of the isolated Receptor Binding Domain (RBD) of Omicron’s spike protein is examined in detail. The parent Omicron lineage has over ten mutations in the ACE2 binding region of the RBD that are specifically associated with its β hairpin loop domain. It is demonstrated through biophysical molecular computations that the mutations in the β hairpin loop domain significantly increase the intra-protein interaction energies of intra-loop and loop–RBD interactions. The interaction energy increases include the formation of new hydrogen bonds in the β hairpin loop domain that help stabilize this critical ACE2 binding region. Our results also agree with recent experiments on the stability of Omicron’s core β barrel domain, outside of its loop domain, and help demonstrate the overall conformational stability of the Omicron RBD. It is further shown here through dynamic simulations that the unbound state of the Omicron RBD remains closely aligned with the bound state configuration, which was not observed for the wild-type RBD. Overall, these studies demonstrate the significantly increased conformational stability of Omicron over its wild-type configuration and raise a number of questions on whether conformational stability could be a positive selection feature of SARS-CoV-2 viral mutational changes. Full article

(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 3rd Edition)

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Graphical abstract

22 pages, 4111 KiB

Open AccessArticle

Exploring Cannabinoids as Potential Inhibitors of SARS-CoV-2 Papain-like Protease: Insights from Computational Analysis and Molecular Dynamics Simulations

by Jamie Holmes, Shahidul M. Islam and Kimberly A. Milligan

Viruses 2024, 16(6), 878; https://doi.org/10.3390/v16060878 - 30 May 2024

Viewed by 1459

Abstract

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global COVID-19 pandemic, challenging healthcare systems worldwide. Effective therapeutic strategies against this novel coronavirus remain limited, underscoring the urgent need for innovative approaches. The present research investigates the potential [...] Read more.

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global COVID-19 pandemic, challenging healthcare systems worldwide. Effective therapeutic strategies against this novel coronavirus remain limited, underscoring the urgent need for innovative approaches. The present research investigates the potential of cannabis compounds as therapeutic agents against SARS-CoV-2 through their interaction with the virus’s papain-like protease (PLpro) protein, a crucial element in viral replication and immune evasion. Computational methods, including molecular docking and molecular dynamics (MD) simulations, were employed to screen cannabis compounds against PLpro and analyze their binding mechanisms and interaction patterns. The results showed cannabinoids with binding affinities ranging from −6.1 kcal/mol to −4.6 kcal/mol, forming interactions with PLpro. Notably, Cannabigerolic and Cannabidiolic acids exhibited strong binding contacts with critical residues in PLpro’s active region, indicating their potential as viral replication inhibitors. MD simulations revealed the dynamic behavior of cannabinoid–PLpro complexes, highlighting stable binding conformations and conformational changes over time. These findings shed light on the mechanisms underlying cannabis interaction with SARS-CoV-2 PLpro, aiding in the rational design of antiviral therapies. Future research will focus on experimental validation, optimizing binding affinity and selectivity, and preclinical assessments to develop effective treatments against COVID-19. Full article

(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 3rd Edition)

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15 pages, 2838 KiB

Open AccessArticle

Distribution of SARS-CoV-2 Genomes in Wastewaters and the Associated Potential Infection Risk for Plant Workers in Typical Urban and Peri-Urban Communities of the Buffalo City Region, South Africa

by Balisa Ngqwala, Luyanda Msolo, Kingsley Ehi Ebomah, Nolonwabo Nontongana and Anthony Ifeanyi Okoh

Viruses 2024, 16(6), 871; https://doi.org/10.3390/v16060871 - 29 May 2024

Viewed by 796

Abstract

The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in wastewater has been reported in several studies and similar research can be used as a proxy for an early warning of potential Coronavirus disease 2019 (COVID-19) outbreaks. This study focused on profiling [...] Read more.

The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in wastewater has been reported in several studies and similar research can be used as a proxy for an early warning of potential Coronavirus disease 2019 (COVID-19) outbreaks. This study focused on profiling the incidence of SARS-CoV-2 genomes in wastewater samples obtained from facilities located in the Buffalo City Municipality. Raw samples were collected weekly using the grab technique for a period of 48 weeks. Ribonucleic acids were extracted from the samples, using the QIAGEN Powersoil Total RNA Extraction kit, and extracted RNA samples were further profiled for the presence of SARS-CoV-2 genomes using Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) technique. Furthermore, various environmental matrices were utilized to estimate the potential health risk to plant operators associated with exposure to SARS-CoV-2 viral particles using the quantitative microbiological risk assessment (QMRA) model. Our findings revealed the prevalence of SARS-CoV-2 genomes with concentrations that ranged from 0.22

\times 10^{3}

to 17.60

\times 10^{3}

genome copies per milliliter (GC/mL). Different exposure scenarios were employed for the QMRA model, and the findings indicate a probability of infection (P(i)) ranging from 0.93% to 37.81% across the study sites. Similarly, the P(i) was highly significant (p < 0.001) for the 20 mL volumetric intake as compared to other volumetric intake scenarios, and high P(i) was also observed in spring, autumn, and winter for all WWTPs. The P(i) was significantly different (p < 0.05) with respect to the different seasons and with respect to different volume scenarios. Full article

(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 3rd Edition)

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Review

Jump to: Research, Other

14 pages, 939 KiB

Open AccessReview

Neurological Complications of COVID-19: Unraveling the Pathophysiological Underpinnings and Therapeutic Implications

by Ashutosh Vashisht, Vishakha Vashisht, Harmanpreet Singh, Pankaj Ahluwalia, Ashis K. Mondal, Colin Williams, Jaspreet Farmaha, Jana Woodall and Ravindra Kolhe

Viruses 2024, 16(8), 1183; https://doi.org/10.3390/v16081183 - 24 Jul 2024

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19), induced a global pandemic with a diverse array of clinical manifestations. While the acute phase of the pandemic may be waning, the intricacies of COVID-19′s impact on neurological health [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19), induced a global pandemic with a diverse array of clinical manifestations. While the acute phase of the pandemic may be waning, the intricacies of COVID-19′s impact on neurological health remain a crucial area of investigation. Early recognition of the spectrum of COVID-19 symptoms, ranging from mild fever and cough to life-threatening respiratory distress and multi-organ failure, underscored the significance of neurological complications, including anosmia, seizures, stroke, disorientation, encephalopathy, and paralysis. Notably, patients requiring intensive care unit (ICU) admission due to neurological challenges or due to them exhibiting neurological abnormalities in the ICU have shown increased mortality rates. COVID-19 can lead to a range of neurological complications such as anosmia, stroke, paralysis, cranial nerve deficits, encephalopathy, delirium, meningitis, seizures, etc., in affected patients. This review elucidates the burgeoning landscape of neurological sequelae associated with SARS-CoV-2 infection and explores the underlying neurobiological mechanisms driving these diverse manifestations. A meticulous examination of potential neuroinvasion routes by SARS-CoV-2 underscores the intricate interplay between the virus and the nervous system. Moreover, we dissect the diverse neurological manifestations emphasizing the necessity of a multifaceted approach to understanding the disease’s neurological footprint. In addition to elucidating the pathophysiological underpinnings, this review surveys current therapeutic modalities and delineates prospective avenues for neuro-COVID research. By integrating epidemiological, clinical, and diagnostic parameters, we endeavor to foster a comprehensive analysis of the nexus between COVID-19 and neurological health, thereby laying the groundwork for targeted therapeutic interventions and long-term management strategies. Full article

(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 3rd Edition)

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19 pages, 1768 KiB

Open AccessReview

SARS-CoV-2 Omicron: Viral Evolution, Immune Evasion, and Alternative Durable Therapeutic Strategies

by Hailong Guo, Sha Ha, Jason W. Botten, Kai Xu, Ningyan Zhang, Zhiqiang An, William R. Strohl, John W. Shiver and Tong-Ming Fu

Viruses 2024, 16(5), 697; https://doi.org/10.3390/v16050697 - 28 Apr 2024

Cited by 1 | Viewed by 2275

Abstract

Since the SARS-CoV-2 Omicron virus has gained dominance worldwide, its continual evolution with unpredictable mutations and patterns has revoked all authorized immunotherapeutics. Rapid viral evolution has also necessitated several rounds of vaccine updates in order to provide adequate immune protection. It remains imperative [...] Read more.

Since the SARS-CoV-2 Omicron virus has gained dominance worldwide, its continual evolution with unpredictable mutations and patterns has revoked all authorized immunotherapeutics. Rapid viral evolution has also necessitated several rounds of vaccine updates in order to provide adequate immune protection. It remains imperative to understand how Omicron evolves into different subvariants and causes immune escape as this could help reevaluate the current intervention strategies mostly implemented in the clinics as emergency measures to counter the pandemic and, importantly, develop new solutions. Here, we provide a review focusing on the major events of Omicron viral evolution, including the features of spike mutation that lead to immune evasion against monoclonal antibody (mAb) therapy and vaccination, and suggest alternative durable options such as the ACE2-based experimental therapies superior to mAbs to address this unprecedented evolution of Omicron virus. In addition, this type of unique ACE2-based virus-trapping molecules can counter all zoonotic SARS coronaviruses, either from unknown animal hosts or from established wild-life reservoirs of SARS-CoV-2, and even seasonal alpha coronavirus NL63 that depends on human ACE2 for infection. Full article

(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 3rd Edition)

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Other

Jump to: Research, Review

9 pages, 2220 KiB

Open AccessBrief Report

Transmission Patterns of Co-Circulation of Omicron Sub-Lineages in Hong Kong SAR, China, a City with Rigorous Social Distancing Measures, in 2022

by Ning Chow, Teng Long, Lam-Kwong Lee, Ivan Tak-Fai Wong, Annie Wing-Tung Lee, Wing-Yin Tam, Harmen Fung-Tin Wong, Jake Siu-Lun Leung, Franklin Wang-Ngai Chow, Kristine Shik Luk, Alex Yat-Man Ho, Jimmy Yiu-Wing Lam, Miranda Chong-Yee Yau, Tak-Lun Que, Kam-Tong Yip, Viola Chi-Ying Chow, River Chun-Wai Wong, Bobo Wing-Yee Mok, Hong-lin Chen and Gilman Kit-Hang Siu

Viruses 2024, 16(6), 981; https://doi.org/10.3390/v16060981 - 18 Jun 2024

Viewed by 1297

Abstract

Objective: This study aimed to characterize the changing landscape of circulating SARS-CoV-2 lineages in the local community of Hong Kong throughout 2022. We examined how adjustments to quarantine arrangements influenced the transmission pattern of Omicron variants in a city with relatively rigorous social [...] Read more.

Objective: This study aimed to characterize the changing landscape of circulating SARS-CoV-2 lineages in the local community of Hong Kong throughout 2022. We examined how adjustments to quarantine arrangements influenced the transmission pattern of Omicron variants in a city with relatively rigorous social distancing measures at that time. Methods: In 2022, a total of 4684 local SARS-CoV-2 genomes were sequenced using the Oxford Nanopore GridION sequencer. SARS-CoV-2 consensus genomes were generated by MAFFT, and the maximum likelihood phylogeny of these genomes was determined using IQ-TREE. The dynamic changes in lineages were depicted in a time tree created by Nextstrain. Statistical analysis was conducted to assess the correlation between changes in the number of lineages and adjustments to quarantine arrangements. Results: By the end of 2022, a total of 83 SARS-CoV-2 lineages were identified in the community. The increase in the number of new lineages was significantly associated with the relaxation of quarantine arrangements (One-way ANOVA, F(5, 47) = 18.233, p < 0.001)). Over time, Omicron BA.5 sub-lineages replaced BA.2.2 and became the predominant Omicron variants in Hong Kong. The influx of new lineages reshaped the dynamics of Omicron variants in the community without fluctuating the death rate and hospitalization rate (One-way ANOVA, F(5, 47) = 2.037, p = 0.091). Conclusion: This study revealed that even with an extended mandatory quarantine period for incoming travelers, it may not be feasible to completely prevent the introduction and subsequent community spread of highly contagious Omicron variants. Ongoing molecular surveillance of COVID-19 remains essential to monitor the emergence of new recombinant variants. Full article

(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 3rd Edition)

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