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Pathogens
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SARS-CoV-2: From Virus Replication Cycle to Antiviral Strategies
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SARS-CoV-2: From Virus Replication Cycle to Antiviral Strategies

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 7156

Special Issue Editor

Dr. Pawel Zmora

E-Mail Website
Guest Editor
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland
Interests: emerging viruses; influenza viruses; coronaviruses; virus-host interactions; virus entry; vaccines development; wastewater-based epidemiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

SARS-CoV-2 has already infected 263 million people and the ongoing COVID-19 pandemic has killed more than 5 million people worldwide. To prevent further deaths and minimize the socio-economic burden, the global population must be vaccinated and acquire herd immunity. However, it needs to be highlighted that vaccine effectiveness and protection can be low in some groups (i.e., ‘vaccine non-responders’, immunocompromised patients), and these people can develop severe COVID-19. Moreover, considering the relatively low proportion of vaccinated people, there is a risk of the emergence of new potential vaccine-resistant SARS-CoV-2 strains. Therefore, in addition to vaccination, efficient drugs for COVID-19 treatment need to be developed.

Knowledge of the viral replication cycle and virus–host interaction is key to developing novel antivirals. Thus, this Pathogens Special Issue will focus on SARS-CoV-2 biology, including virus entry, replication, assembly and release, as well as SARS-CoV-2–host cell interactions, and potential implications for the development of novel antiviral strategies.

Dr. Pawel Zmora
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • SARS-CoV-2
  • virus entry
  • virus replication
  • virus assembly and budding
  • antivirals

Published Papers (4 papers)

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Research

14 pages, 6487 KiB  
Article
Genomic Mutations in SARS-CoV-2 Genome following Infection in Syrian Golden Hamster and Associated Lung Pathologies
by Gudepalya Renukaiah Rudramurthy, Chakenahalli N. Naveenkumar, Kumaraswamy Bharathkumar, Radha K. Shandil and Shridhar Narayanan
Pathogens 2023, 12(11), 1328; https://doi.org/10.3390/pathogens12111328 - 8 Nov 2023
Cited by 1 | Viewed by 890
Abstract
The continuous evolution of the SARS-CoV-2 virus led to constant developments and efforts in understanding the significance and impacts of SARS-CoV-2 variants on human health. Our study aimed to determine the accumulation of genetic mutations and associated lung pathologies in male and female [...] Read more.
The continuous evolution of the SARS-CoV-2 virus led to constant developments and efforts in understanding the significance and impacts of SARS-CoV-2 variants on human health. Our study aimed to determine the accumulation of genetic mutations and associated lung pathologies in male and female hamsters infected with the ancestral Wuhan strain of SARS-CoV-2. The present study showed no significant difference in the viral load between male and female hamsters and peak infection was found to be on day four post infection in both sexes of the animals. Live virus particles were detected up to 5 days post infection (dpi) through the TCID-50 assay, while qRT-PCR could detect viral RNA up to 14 dpi from all the infected animals. Further, the determination of the neutralizing antibody titer showed the onset of the humoral immune response as early as 4 dpi in both sexes against SARS-CoV-2, and a significant cross-protection against the delta variant of SARS-CoV-2 was observed. Histopathology showed edema, inflammation, inflammatory cell infiltration, necrosis, and degeneration of alveolar and bronchial epithelium cells from 3 dpi to 14 dpi in both sexes. Furthermore, next-generation sequencing (NGS) showed up to 10 single-nucleotide polymorphisms (SNPs) in the SARS-CoV-2 (ancestral Wuhan strain) genome isolated from both male and female hamsters. The mutation observed at the 23014 position (Glu484Asp) in the SARS-CoV-2 genome isolated from both sexes of the hamsters plays a significant role in the antiviral efficacy of small molecules, vaccines, and the Mabs-targeting S protein. The present study shows that either of the genders can be used in the pre-clinical efficacy of antiviral agents against SARS-CoV-2 in hamsters. However, considering the major mutation in the S protein, the understanding of the genetic mutation in SARS-CoV-2 after passing through hamsters is crucial in deciding the efficacy of the antiviral agents targeting the S protein. Importance: Our study findings indicate the accumulation of genomic mutations in SARS-CoV-2 after passing through the Syrian golden hamsters. Understanding the genomic mutations showed that either of the hamster genders can be used in the pre-clinical efficacy of antiviral agents and vaccines. Full article
(This article belongs to the Special Issue SARS-CoV-2: From Virus Replication Cycle to Antiviral Strategies)
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13 pages, 2275 KiB  
Article
Novel Molecular Consortia of Cannabidiol with Nonsteroidal Anti-Inflammatory Drugs Inhibit Emerging Coronaviruses’ Entry
by Anna Pawełczyk, Rafał Nowak, Monika Gazecka, Anna Jelińska, Lucjusz Zaprutko and Paweł Zmora
Pathogens 2023, 12(7), 951; https://doi.org/10.3390/pathogens12070951 - 18 Jul 2023
Viewed by 2131
Abstract
The COVID-19 pandemic provoked a global health crisis and highlighted the need for new therapeutic strategies. In this study, we explore the potential of the molecular consortia of cannabidiol (CBD) and non-steroidal anti-inflammatory drugs (NSAIDs) as novel antiviral dual-target agents against SARS-CoV-2/COVID-19. CBD [...] Read more.
The COVID-19 pandemic provoked a global health crisis and highlighted the need for new therapeutic strategies. In this study, we explore the potential of the molecular consortia of cannabidiol (CBD) and non-steroidal anti-inflammatory drugs (NSAIDs) as novel antiviral dual-target agents against SARS-CoV-2/COVID-19. CBD is a natural compound with a wide range of therapeutic activities, including antiviral and anti-inflammatory properties, while NSAIDs are commonly used to mitigate the symptoms of viral infections. Chemical modifications of CBD with NSAIDs were performed to obtain dual-target agents with enhanced activity against SARS-CoV-2. The synthesised compounds were characterised using spectroscopic techniques. The biological activity of three molecular consortia (CBD–ibuprofen, CBD–ketoprofen, and CBD–naproxen) was evaluated in cell lines transduced with vesicular stomatitis virus-based pseudotypes bearing the SARS-CoV-1 or SARS-CoV-2 spike proteins or infected with influenza virus A/Puerto Rico/8/34. The results showed that some CBD–NSAID molecular consortia have superior antiviral activity against SARS-CoV-1 and SARS-CoV-2, but not against the influenza A virus. This may suggest a potential therapeutic role for these compounds in the treatment of emerging coronavirus infections. Further studies are needed to investigate the efficacy of these compounds in vivo, and their potential use in clinical settings. Our findings provide a promising new approach to combatting current and future viral emergencies. Full article
(This article belongs to the Special Issue SARS-CoV-2: From Virus Replication Cycle to Antiviral Strategies)
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Graphical abstract

11 pages, 2157 KiB  
Article
Hydroxypropyl-β-Cyclodextrin Depletes Membrane Cholesterol and Inhibits SARS-CoV-2 Entry into HEK293T-ACEhi Cells
by Silvia Alboni, Valentina Secco, Bianca Papotti, Antonietta Vilella, Maria Pia Adorni, Francesca Zimetti, Laurent Schaeffer, Fabio Tascedda, Michele Zoli, Pascal Leblanc and Erica Villa
Pathogens 2023, 12(5), 647; https://doi.org/10.3390/pathogens12050647 - 27 Apr 2023
Cited by 2 | Viewed by 1692
Abstract
Vaccination has drastically decreased mortality due to coronavirus disease 19 (COVID-19), but not the rate of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Alternative strategies such as inhibition of virus entry by interference with angiotensin-I-converting enzyme 2 (ACE2) receptors could be warranted. Cyclodextrins [...] Read more.
Vaccination has drastically decreased mortality due to coronavirus disease 19 (COVID-19), but not the rate of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Alternative strategies such as inhibition of virus entry by interference with angiotensin-I-converting enzyme 2 (ACE2) receptors could be warranted. Cyclodextrins (CDs) are cyclic oligosaccharides that are able to deplete cholesterol from membrane lipid rafts, causing ACE2 receptors to relocate to areas devoid of lipid rafts. To explore the possibility of reducing SARS-CoV-2 entry, we tested hydroxypropyl-β-cyclodextrin (HPβCD) in a HEK293T-ACE2hi cell line stably overexpressing human ACE2 and Spike-pseudotyped SARS-CoV-2 lentiviral particles. We showed that HPβCD is not toxic to the cells at concentrations up to 5 mM, and that this concentration had no significant effect on cell cycle parameters in any experimental condition tested. Exposure of HEK293T-ACEhi cells to concentrations of HPβCD starting from 2.5 mM to 10 mM showed a concentration-dependent reduction of approximately 50% of the membrane cholesterol content. In addition, incubation of HEK293T-ACEhi cells with HIV-S-CoV-2 pseudotyped particles in the presence of increasing concentrations of HPβCD (from 0.1 to 10 mM) displayed a concentration-dependent effect on SARS-CoV-2 entry efficiency. Significant effects were detected at concentrations at least one order of magnitude lower than the lowest concentration showing toxic effects. These data indicate that HPβCD is a candidate for use as a SARS-CoV-2 prophylactic agent. Full article
(This article belongs to the Special Issue SARS-CoV-2: From Virus Replication Cycle to Antiviral Strategies)
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17 pages, 9214 KiB  
Article
SARS-CoV-2 Exploits Non-Canonical Autophagic Processes to Replicate, Mature, and Egress the Infected Vero E6 Cells
by Juraj Koči, Marta Novotová, Monika Sláviková, Boris Klempa and Ivan Zahradník
Pathogens 2022, 11(12), 1535; https://doi.org/10.3390/pathogens11121535 - 14 Dec 2022
Cited by 1 | Viewed by 1605
Abstract
The coronavirus transforms the cytoplasm of susceptible cells to support virus replication. It also activates autophagy-like processes, the role of which is not well understood. Here, we studied SARS-CoV-2-infected Vero E6 cells using transmission electron microscopy and autophagy PCR array. After 6–24 h [...] Read more.
The coronavirus transforms the cytoplasm of susceptible cells to support virus replication. It also activates autophagy-like processes, the role of which is not well understood. Here, we studied SARS-CoV-2-infected Vero E6 cells using transmission electron microscopy and autophagy PCR array. After 6–24 h post-infection (hpi), the cytoplasm of infected cells only contained double-membrane vesicles, phagophores, and phagosomes engulfing virus particles and cytoplasmic debris, including damaged mitochondria. The phagosomes interacted with the viral nucleoprotein complex, virus particles, mitochondria, and lipid droplets. The phagosomes transformed into egress vacuoles, which broke through the plasmalemma and discharged the virus particles. The Vero E6 cells exhibited pronounced virus replication at 6 hpi, which stabilized at 18–24 hpi at a high level. The autophagy PCR array tests revealed a significant upregulation of 10 and downregulation of 8 autophagic gene markers out of 84. Altogether, these results underline the importance of autophagy-like processes for SARS-CoV-2 maturation and egress, and point to deviations from a canonical autophagy response. Full article
(This article belongs to the Special Issue SARS-CoV-2: From Virus Replication Cycle to Antiviral Strategies)
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