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COVID
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Advances in Coronaviruses Research: Pathogenesis, Immunity, and Antivirals
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Advances in Coronaviruses Research: Pathogenesis, Immunity, and Antivirals

A special issue of COVID (ISSN 2673-8112). This special issue belongs to the section "Human or Animal Coronaviruses".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 11449

Special Issue Editor

Dr. Nadine Alvarez

E-Mail Website
Guest Editor
Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA
Interests: human respiratory pathogens; lung infections; viral and bacterial infectious diseases; drug development; translational research

Special Issue Information

Dear Colleagues,

Five years have passed since the outbreak of SARS-CoV-2, which triggered the most recent global pandemic and significantly impacted public health worldwide. According to a World Health Organization (WHO) report released in August 2025, COVID-19 has resulted in over 778 million confirmed cases and more than 7 million deaths globally. The Centers for Disease Control and Prevention (CDC) continues to monitor emerging variants; the latest surveillance has identified a new variant, XFG, which currently accounts for an estimated 78% of cases in the United States.

Despite the availability of effective prophylactic vaccines and therapeutic options, SARS-CoV-2 continues to evolve. New subvariants are emerging and circulating, characterized by key mutations that primarily enhance transmissibility and immune evasion. Ongoing research into the virus’s pathogenesis and mechanisms of immune escape has led to the discovery of novel antiviral agents, some of which show strong potential and are progressing through various stages of development.

The Special Issue "Advances in Coronaviruses Research: Pathogenesis, Immunity, and Antivirals" has been updated to reflect recent breakthroughs in the field. In addition to covering the discovery and development of new antiviral candidates, this issue aims to showcase a broader spectrum of innovative therapeutic strategies. We invite research articles, short communications, and reviews that explore cutting-edge approaches such as nanotechnologies, monoclonal antibodies, genome editing, and other alternatives aimed at inhibiting viral replication. Contributions that provide new insights into viral adaptation, immune evasion, and pathogenesis are also highly encouraged.

Dr. Nadine Alvarez
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 250 words) can be sent to the Editorial Office for assessment.

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. COVID 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 1200 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

  • pan-coronavirus
  • antivirals
  • viral pathogenesis
  • host-interactions
  • immunity
  • novel and advanced therapeutics
  • drug discovery

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (3 papers)

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Research

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13 pages, 845 KB  
Article
Characterization of the SARS-CoV-2 Mutation Pattern Generated In Vitro by the Antiviral Action of Lycorine
by Silvina Soledad Maidana, Sonia Alejandra Romera, Ana Marandino, Rocío Lucia Tau, Juan Mauel Shammas, Yanina Panzera and Ruben Pérez
COVID 2025, 5(11), 181; https://doi.org/10.3390/covid5110181 - 23 Oct 2025
Viewed by 971
Abstract
SARS-CoV-2 persists worldwide, driving the demand for effective antivirals that inhibit replication and limit the emergence of resistant variants. Lycorine, a non-nucleoside inhibitor of SARS-CoV-2 RNA-dependent RNA polymerase, exhibits antiviral activity without direct mutagenic effects. Here, we examine the occurrence of single-nucleotide variants [...] Read more.
SARS-CoV-2 persists worldwide, driving the demand for effective antivirals that inhibit replication and limit the emergence of resistant variants. Lycorine, a non-nucleoside inhibitor of SARS-CoV-2 RNA-dependent RNA polymerase, exhibits antiviral activity without direct mutagenic effects. Here, we examine the occurrence of single-nucleotide variants (SNVs) and insertions/deletions (indels) in SARS-CoV-2 B.1.499 strain during serial passages in Vero cells, comparing lycorine-treated cultures (2.5 and 5 µg/mL) with untreated controls. Whole-genome sequencing was used to assess mutation patterns and frequencies. Lycorine-treated passages displayed greater variant diversity than controls, with fixed mutations mainly affecting non-structural proteins (Nsp3-F1375A, Nsp5-L50F, and Nsp14-G265D) and the envelope protein (E-S6L). A 15-nucleotide deletion in the spike gene (QTQTN motif) occurred in both groups but became fixed only in untreated passages, suggesting negative selection under lycorine pressure. Notably, the L50F mutation in Nsp5, previously linked to nirmatrelvir resistance, was found exclusively in lycorine-treated passages. Additionally, a 1-nucleotide deletion in the accessory gene ORF8, detected only under lycorine treatment, resulted in a frameshift mutation that added four amino acids, potentially altering the protein’s function. Overall, lycorine induces a distinct mutation profile, favoring replication-related variants while suppressing deleterious deletions. These findings suggest potential mechanisms of cross-resistance and highlight the importance of monitoring resistance during clinical use. Full article
(This article belongs to the Special Issue Advances in Coronaviruses Research: Pathogenesis, Immunity, and Antivirals)
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18 pages, 6130 KB  
Article
The Antiviral Activity of GcMAF in the Treatment of Experimental Animals Infected with SARS-CoV-2
by Anastasia S. Proskurina, Oleg S. Taranov, Svetlana S. Kirikovich, Svetlana V. Aidagulova, Elena K. Ivleva, Andrey V. Shipovalov, Gleb A. Kudrov, Sergei A. Bodnev, Alena S. Ovchinnikova, Anna V. Zaykovskaya, Oleg V. Pyankov, Evgeniy V. Levites, Genrikh S. Ritter, Vera S. Ruzanova, Sofya G. Oshikhmina, Evgeniya V. Dolgova, Evgeniy L. Zavjalov, Alexandr A. Ostanin, Elena R. Chernykh, Nikolay A. Kolchanov and Sergey S. Bogachevadd Show full author list remove Hide full author list
COVID 2025, 5(3), 36; https://doi.org/10.3390/covid5030036 - 8 Mar 2025
Viewed by 2488
Abstract
Despite the end of the COVID-19 pandemic, there still remain risks of new aggressive strains of coronavirus. As the human population increases progressively, it is mandatory to ensure both preventive measures and an immediate response to emerging infectious threats. Another essential component for [...] Read more.
Despite the end of the COVID-19 pandemic, there still remain risks of new aggressive strains of coronavirus. As the human population increases progressively, it is mandatory to ensure both preventive measures and an immediate response to emerging infectious threats. Another essential component for rapidly restraining a new possible pandemic is the development of new anticoronaviral therapeutics. In the present study, the anticoronaviral capabilities of Gc protein-derived macrophage-activating factor (GcMAF) are characterized. It is demonstrated that the administration of GcMAF to Syrian hamsters infected with SARS-CoV-2 within the first phase of infection (six days postinfection) is accompanied by (i) a statistically significant reduction in the viral load of the lung tissue and (ii) the switching of the inflammatory status of the lung tissue to a neutral one in terms of mRNA expression levels of the groups of pro/anti-inflammatory cytokines and chemokines. The potential mechanism for this antiviral action and the containment of the inflammatory response by the drug associated with the engagement of terminal N-acetylgalactosamine GcMAF and C-type lectin domain containing 10A expressed at the surface of lung-infiltrating macrophages and pneumocytes, which simultaneously express angiotensin-converting enzyme 2, is discussed. Full article
(This article belongs to the Special Issue Advances in Coronaviruses Research: Pathogenesis, Immunity, and Antivirals)
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Review

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24 pages, 1795 KB  
Review
SARS-CoV-2 Replication Revisited: Molecular Insights and Current and Emerging Antiviral Strategies
by Bryan John J. Subong and Imelda L. Forteza
COVID 2025, 5(6), 85; https://doi.org/10.3390/covid5060085 - 30 May 2025
Cited by 5 | Viewed by 6686
Abstract
The replication machinery of SARS-CoV-2 is a primary target for therapeutic intervention, and has led to significant progress in antiviral medication discovery. This review consolidates contemporary molecular insights into viral replication and rigorously assesses treatment methods at different phases of viruses’ clinical development. [...] Read more.
The replication machinery of SARS-CoV-2 is a primary target for therapeutic intervention, and has led to significant progress in antiviral medication discovery. This review consolidates contemporary molecular insights into viral replication and rigorously assesses treatment methods at different phases of viruses’ clinical development. Direct-acting antivirals, such as nucleoside analogs (e.g., remdesivir, molnupiravir) and protease inhibitors (e.g., nirmatrelvir), have shown clinical effectiveness in diminishing morbidity and hospitalization rates. Simultaneously, host-targeted medicines like baricitinib, camostat, and brequinar leverage critical host–virus interactions, providing additional pathways to reduce viral replication while possibly minimizing the development of resistance. Notwithstanding these advancements, constraints in distribution methods, antiviral longevity, and the risk of mutational evasion demand novel strategies. Promising investigational approaches encompass CRISPR-mediated RNA degradation systems, inhalable siRNA-nanoparticle conjugates, and molecular glue degraders that target host and viral proteins. Furthermore, next-generation treatments aimed at underutilized enzyme domains (e.g., NiRAN, ExoN) and host chaperone systems (e.g., TRiC complex) signify a transformative approach in antiviral targeting. The integration of high-throughput phenotypic screening, AI-driven medication repurposing, and systems virology is transforming the antiviral discovery field. An ongoing interdisciplinary endeavor is necessary to convert these findings into versatile, resistance-resistant antiviral strategies that are applicable beyond the present pandemic and in future coronavirus epidemics. Full article
(This article belongs to the Special Issue Advances in Coronaviruses Research: Pathogenesis, Immunity, and Antivirals)
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