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Molecular Research in Emerging Viruses 2020

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 45800

Special Issue Editors

State Key Laboratory of Emerging Infectious Diseases, Research Centre of Infection and Immunology and Carol Yu Centre for Infection, University of Hong Kong, Hong Kong, China
Interests: emerging infectious diseases; novel pathogen discovery; pathogen genomics and evolution; interspecies transmission of zoonotic viruses
Special Issues, Collections and Topics in MDPI journals
Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University, Collins, CO, USA
Interests: rodent- and bat-borne viruses
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Viruses are increasingly important in causing various infectious diseases in both humans and animals. Some viruses, especially zoonotic viruses, can also evolve rapidly to generate new variants with enhanced virulence that may emerge or re-emerge to cause epidemics. Examples of these viruses include Zika virus, Ebola virus, avian influenza viruses, and Middle East Respiratory Coronavirus. These are good examples showing how new viruses or variants can cause huge public health problems and economic losses within a short time. On the other hand, old viruses, such as African swine fever virus, measles virus, and Dengue virus, have emerged or re-emerged, as a result of various reasons such as global warming and cross-country trafficking of humans and animals. With the limitations of viral cultures and serological tests, the diagnosis of viral infections often relies on molecular assays. Unlike bacterial and fungal diseases, which can be treated with antibiotics or antifungals, effective antivirals are lacking for many viruses. Since viruses take hold of host machinery for their replication, the identification of antiviral targets can be difficult. Vaccines for many of these emerging viruses are also lacking. Therefore, new research directions are crucial to predict, prevent, and combat virus diseases.

This Special Issue will include manuscripts on different aspects of virus diseases in both humans and animals. Papers aiming to improve our understanding of viral evolution and pathogenesis; mechanisms of virus entry; and diagnosis, prevention, and treatment outcomes, especially those focusing on recently emerging or re-emerging viruses, are most welcome.

Closed Special Issue: "Molecular Research in Emerging Viruses 2019"

Prof. Dr. Susanna K. P. Lau
Guest Editor

Dr. Franklin W.N. Chow
Dr. Tony Schountz
Co-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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • Virus
  • Infectious diseases
  • Emerging
  • Epidemics
  • Evolution
  • Diagnostic
  • Pathogenesis
  • Antiviral

Published Papers (6 papers)

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Research

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10 pages, 1497 KiB  
Article
Improved Detection of Antibodies against SARS-CoV-2 by Microsphere-Based Antibody Assay
by Carol Ho-Yan Fong, Jian-Piao Cai, Thrimendra Kaushika Dissanayake, Lin-Lei Chen, Charlotte Yee-Ki Choi, Lok-Hin Wong, Anthony Chin-Ki Ng, Polly K. P. Pang, Deborah Tip-Yin Ho, Rosana Wing-Shan Poon, Tom Wai-Hin Chung, Siddharth Sridhar, Kwok-Hung Chan, Jasper Fuk-Woo Chan, Ivan Fan-Ngai Hung, Kwok-Yung Yuen and Kelvin Kai-Wang To
Int. J. Mol. Sci. 2020, 21(18), 6595; https://doi.org/10.3390/ijms21186595 - 09 Sep 2020
Cited by 16 | Viewed by 3125
Abstract
Currently available COVID-19 antibody tests using enzyme immunoassay (EIA) or immunochromatographic assay have variable sensitivity and specificity. Here, we developed and evaluated a novel microsphere-based antibody assay (MBA) for detecting immunoglobulin G (IgG) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein (NP) [...] Read more.
Currently available COVID-19 antibody tests using enzyme immunoassay (EIA) or immunochromatographic assay have variable sensitivity and specificity. Here, we developed and evaluated a novel microsphere-based antibody assay (MBA) for detecting immunoglobulin G (IgG) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein (NP) and spike protein receptor binding domain (RBD). The seropositive cutoff value was set using a cohort of 294 anonymous serum specimens collected in 2018. The specificity was assessed using serum specimens collected from organ donors or influenza patients before 2020. Seropositive rate was determined among COVID-19 patients. Time-to-seropositivity and signal-to-cutoff (S/CO) ratio were compared between MBA and EIA. MBA had a specificity of 100% (93/93; 95% confidence interval (CI), 96–100%) for anti-NP IgG, 98.9% (92/93; 95% CI 94.2–100%) for anti-RBD IgG. The MBA seropositive rate for convalescent COVID-19 patients was 89.8% (35/39) for anti-NP IgG and 79.5% (31/39) for anti-RBD IgG. The time-to-seropositivity was shorter with MBA than EIA. MBA could better differentiate between COVID-19 patients and negative controls with higher S/CO ratio for COVID-19 patients, lower S/CO ratio with negative controls and fewer specimens in the equivocal range. MBA is robust, simple and is suitable for clinical microbiology laboratory for the accurate determination of anti-SARS-CoV-2 antibodies for diagnosis, serosurveillance, and vaccine trials. Full article
(This article belongs to the Special Issue Molecular Research in Emerging Viruses 2020)
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10 pages, 1273 KiB  
Article
A Rapid, Simple, Inexpensive, and Mobile Colorimetric Assay COVID-19-LAMP for Mass On-Site Screening of COVID-19
by Franklin Wang-Ngai Chow, Tony Tat-Yin Chan, Anthony Raymond Tam, Suhui Zhao, Weiming Yao, Joshua Fung, Flora Ka-Kei Cheng, George Chi-Shing Lo, Stella Chu, Kam Leng Aw-Yong, James Yat-Man Tang, Chi-Ching Tsang, Hayes Kam-Hei Luk, Antonio Cheuk-Pui Wong, Kenneth Sze-Ming Li, Longchao Zhu, Zirong He, Emily Wan Ting Tam, Tom Wai-Hin Chung, Sally Cheuk Ying Wong, Tak-Lun Que, Kitty Sau-Chun Fung, David Christopher Lung, Alan Ka-Lun Wu, Ivan Fan-Ngai Hung, Patrick Chiu-Yat Woo and Susanna Kar-Pui Lauadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2020, 21(15), 5380; https://doi.org/10.3390/ijms21155380 - 29 Jul 2020
Cited by 77 | Viewed by 8267
Abstract
To control the COVID-19 pandemic and prevent its resurgence in areas preparing for a return of economic activities, a method for a rapid, simple, and inexpensive point-of-care diagnosis and mass screening is urgently needed. We developed and evaluated a one-step colorimetric reverse-transcriptional loop-mediated [...] Read more.
To control the COVID-19 pandemic and prevent its resurgence in areas preparing for a return of economic activities, a method for a rapid, simple, and inexpensive point-of-care diagnosis and mass screening is urgently needed. We developed and evaluated a one-step colorimetric reverse-transcriptional loop-mediated isothermal amplification assay (COVID-19-LAMP) for detection of SARS-CoV-2, using SARS-CoV-2 isolate and respiratory samples from patients with COVID-19 (n = 223) and other respiratory virus infections (n = 143). The assay involves simple equipment and techniques and low cost, without the need for expensive qPCR machines, and the result, indicated by color change, is easily interpreted by naked eyes. COVID-19-LAMP can detect SARS-CoV-2 RNA with detection limit of 42 copies/reaction. Of 223 respiratory samples positive for SARS-CoV-2 by qRT-PCR, 212 and 219 were positive by COVID-19-LAMP at 60 and 90 min (sensitivities of 95.07% and 98.21%) respectively, with the highest sensitivities among nasopharyngeal swabs (96.88% and 98.96%), compared to sputum/deep throat saliva samples (94.03% and 97.02%), and throat swab samples (93.33% and 98.33%). None of the 143 samples with other respiratory viruses were positive by COVID-19-LAMP, showing 100% specificity. Samples with higher viral load showed shorter detection time, some as early as 30 min. This inexpensive, highly sensitive and specific COVID-19-LAMP assay can be useful for rapid deployment as mobile diagnostic units to resource-limiting areas for point-of-care diagnosis, and for unlimited high-throughput mass screening at borders to reduce cross-regional transmission. Full article
(This article belongs to the Special Issue Molecular Research in Emerging Viruses 2020)
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19 pages, 10990 KiB  
Article
Insertion of Basic Amino Acids in the Hemagglutinin Cleavage Site of H4N2 Avian Influenza Virus (AIV)—Reduced Virus Fitness in Chickens is Restored by Reassortment with Highly Pathogenic H5N1 AIV
by Marcel Gischke, Reiner Ulrich, Olanrewaju I. Fatola, David Scheibner, Ahmed H. Salaheldin, Beate Crossley, Eva Böttcher-Friebertshäuser, Jutta Veits, Thomas C. Mettenleiter and Elsayed M. Abdelwhab
Int. J. Mol. Sci. 2020, 21(7), 2353; https://doi.org/10.3390/ijms21072353 - 28 Mar 2020
Cited by 5 | Viewed by 4901
Abstract
Highly pathogenic (HP) avian influenza viruses (AIVs) are naturally restricted to H5 and H7 subtypes with a polybasic cleavage site (CS) in hemagglutinin (HA) and any AIV with an intravenous pathogenicity index (IVPI) ≥ 1.2. Although only a few non-H5/H7 viruses fulfill the [...] Read more.
Highly pathogenic (HP) avian influenza viruses (AIVs) are naturally restricted to H5 and H7 subtypes with a polybasic cleavage site (CS) in hemagglutinin (HA) and any AIV with an intravenous pathogenicity index (IVPI) ≥ 1.2. Although only a few non-H5/H7 viruses fulfill the criteria of HPAIV; it remains unclear why these viruses did not spread in domestic birds. In 2012, a unique H4N2 virus with a polybasic CS 322PEKRRTR/G329 was isolated from quails in California which, however, was avirulent in chickens. This is the only known non-H5/H7 virus with four basic amino acids in the HACS. Here, we investigated the virulence of this virus in chickens after expansion of the polybasic CS by substitution of T327R (322PEKRRRR/G329) or T327K (322PEKRRKR/G329) with or without reassortment with HPAIV H5N1 and H7N7. The impact of single mutations or reassortment on virus fitness in vitro and in vivo was studied. Efficient cell culture replication of T327R/K carrying H4N2 viruses increased by treatment with trypsin, particularly in MDCK cells, and reassortment with HPAIV H5N1. Replication, virus excretion and bird-to-bird transmission of H4N2 was remarkably compromised by the CS mutations, but restored after reassortment with HPAIV H5N1, although not with HPAIV H7N7. Viruses carrying the H4-HA with or without R327 or K327 mutations and the other seven gene segments from HPAIV H5N1 exhibited high virulence and efficient transmission in chickens. Together, increasing the number of basic amino acids in the H4N2 HACS was detrimental for viral fitness particularly in vivo but compensated by reassortment with HPAIV H5N1. This may explain the absence of non-H5/H7 HPAIV in poultry. Full article
(This article belongs to the Special Issue Molecular Research in Emerging Viruses 2020)
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Review

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36 pages, 3016 KiB  
Review
Can SARS-CoV-2 Virus Use Multiple Receptors to Enter Host Cells?
by Laura Kate Gadanec, Kristen Renee McSweeney, Tawar Qaradakhi, Benazir Ali, Anthony Zulli and Vasso Apostolopoulos
Int. J. Mol. Sci. 2021, 22(3), 992; https://doi.org/10.3390/ijms22030992 - 20 Jan 2021
Cited by 96 | Viewed by 14344
Abstract
The occurrence of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVD-19), represents a catastrophic threat to global health. Protruding from the viral surface is a densely glycosylated spike (S) protein, which engages angiotensin-converting enzyme 2 (ACE2) to [...] Read more.
The occurrence of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVD-19), represents a catastrophic threat to global health. Protruding from the viral surface is a densely glycosylated spike (S) protein, which engages angiotensin-converting enzyme 2 (ACE2) to mediate host cell entry. However, studies have reported viral susceptibility in intra- and extrapulmonary immune and non-immune cells lacking ACE2, suggesting that the S protein may exploit additional receptors for infection. Studies have demonstrated interactions between S protein and innate immune system, including C-lectin type receptors (CLR), toll-like receptors (TLR) and neuropilin-1 (NRP1), and the non-immune receptor glucose regulated protein 78 (GRP78). Recognition of carbohydrate moieties clustered on the surface of the S protein may drive receptor-dependent internalization, accentuate severe immunopathological inflammation, and allow for systemic spread of infection, independent of ACE2. Furthermore, targeting TLRs, CLRs, and other receptors (Ezrin and dipeptidyl peptidase-4) that do not directly engage SARS-CoV-2 S protein, but may contribute to augmented anti-viral immunity and viral clearance, may represent therapeutic targets against COVID-19. Full article
(This article belongs to the Special Issue Molecular Research in Emerging Viruses 2020)
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38 pages, 2319 KiB  
Review
Mapping the SARS-CoV-2–Host Protein–Protein Interactome by Affinity Purification Mass Spectrometry and Proximity-Dependent Biotin Labeling: A Rational and Straightforward Route to Discover Host-Directed Anti-SARS-CoV-2 Therapeutics
by Rosa Terracciano, Mariaimmacolata Preianò, Annalisa Fregola, Corrado Pelaia, Tiziana Montalcini and Rocco Savino
Int. J. Mol. Sci. 2021, 22(2), 532; https://doi.org/10.3390/ijms22020532 - 07 Jan 2021
Cited by 33 | Viewed by 8201
Abstract
Protein–protein interactions (PPIs) are the vital engine of cellular machinery. After virus entry in host cells the global organization of the viral life cycle is strongly regulated by the formation of virus-host protein interactions. With the advent of high-throughput -omics platforms, the mirage [...] Read more.
Protein–protein interactions (PPIs) are the vital engine of cellular machinery. After virus entry in host cells the global organization of the viral life cycle is strongly regulated by the formation of virus-host protein interactions. With the advent of high-throughput -omics platforms, the mirage to obtain a “high resolution” view of virus–host interactions has come true. In fact, the rapidly expanding approaches of mass spectrometry (MS)-based proteomics in the study of PPIs provide efficient tools to identify a significant number of potential drug targets. Generation of PPIs maps by affinity purification-MS and by the more recent proximity labeling-MS may help to uncover cellular processes hijacked and/or altered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), providing promising therapeutic targets. The possibility to further validate putative key targets from high-confidence interactions between viral bait and host protein through follow-up MS-based multi-omics experiments offers an unprecedented opportunity in the drug discovery pipeline. In particular, drug repurposing, making use of already existing approved drugs directly targeting these identified and validated host interactors, might shorten the time and reduce the costs in comparison to the traditional drug discovery process. This route might be promising for finding effective antiviral therapeutic options providing a turning point in the fight against the coronavirus disease-2019 (COVID-19) outbreak. Full article
(This article belongs to the Special Issue Molecular Research in Emerging Viruses 2020)
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28 pages, 1698 KiB  
Review
Betacoronavirus Genomes: How Genomic Information has been Used to Deal with Past Outbreaks and the COVID-19 Pandemic
by Alejandro Llanes, Carlos M. Restrepo, Zuleima Caballero, Sreekumari Rajeev, Melissa A. Kennedy and Ricardo Lleonart
Int. J. Mol. Sci. 2020, 21(12), 4546; https://doi.org/10.3390/ijms21124546 - 26 Jun 2020
Cited by 32 | Viewed by 6070
Abstract
In the 21st century, three highly pathogenic betacoronaviruses have emerged, with an alarming rate of human morbidity and case fatality. Genomic information has been widely used to understand the pathogenesis, animal origin and mode of transmission of coronaviruses in the aftermath of the [...] Read more.
In the 21st century, three highly pathogenic betacoronaviruses have emerged, with an alarming rate of human morbidity and case fatality. Genomic information has been widely used to understand the pathogenesis, animal origin and mode of transmission of coronaviruses in the aftermath of the 2002–2003 severe acute respiratory syndrome (SARS) and 2012 Middle East respiratory syndrome (MERS) outbreaks. Furthermore, genome sequencing and bioinformatic analysis have had an unprecedented relevance in the battle against the 2019–2020 coronavirus disease 2019 (COVID-19) pandemic, the newest and most devastating outbreak caused by a coronavirus in the history of mankind. Here, we review how genomic information has been used to tackle outbreaks caused by emerging, highly pathogenic, betacoronavirus strains, emphasizing on SARS-CoV, MERS-CoV and SARS-CoV-2. We focus on shared genomic features of the betacoronaviruses and the application of genomic information to phylogenetic analysis, molecular epidemiology and the design of diagnostic systems, potential drugs and vaccine candidates. Full article
(This article belongs to the Special Issue Molecular Research in Emerging Viruses 2020)
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