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Molecular Research on Coronavirus: Pathogenic Mechanism, Antiviral Drugs and New Vaccines

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 8418

Special Issue Editor


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Guest Editor
1. National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
2. The Cooperative Innovation Center for Sustainable Pig Production, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
Interests: coronaviruses; nanoparticles; drug delivery; viruses; viral diseases diagnosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The Coronaviridae family includes a large number of viruses affecting humans, farm animals, pet animals, wildlife, and birds. Since coronaviruses have a broad host range and tropism, there is a continuous emergence of new coronaviruses, new serotypes, and variants of the currently known coronaviruses. Some of them might cross the species barrier and infect humans, such as the ongoing SARS-CoV-2 pandemic. Thus, it is important to study the pathogenic mechanism of coronaviruses to better develop antiviral drugs and vaccines.

The scope of this issue may include the following points:

  1. The molecular mechanisms of coronavirus infection and related diseases.
  2. The recent advances in the coronavirus vaccines.
  3. Antivirals against coronaviruses.
  4. Monitoring coronaviruses in wildlife.
  5. The development of some novel diagnostic assays for coronaviruses.
  6. Advances in coronavirus host/tissue tropisms.

Prof. Dr. Wentao Li
Guest Editor

Manuscript Submission Information

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Keywords

  • coronavirus
  • pathogenic mechanism
  • viral entry
  • antiviral drugs
  • vaccines
  • epidemiology
  • animal model

Published Papers (5 papers)

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Research

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14 pages, 4109 KiB  
Article
Generation and Characterization of Monoclonal Antibodies against Swine Acute Diarrhea Syndrome Coronavirus Spike Protein
by Xinyue Zhou, Mengjia Zhang, Hanyu Zhang, Hailong Ma, Jiaru Zhou, Hua Cao, Guanghao Guo, Ningning Ma, Qigai He, Yongle Yang, Yifei Lang, Yaowei Huang and Wentao Li
Int. J. Mol. Sci. 2023, 24(23), 17102; https://doi.org/10.3390/ijms242317102 - 4 Dec 2023
Viewed by 1019
Abstract
Swine acute diarrhea syndrome coronavirus (SADS-CoV), a member of the family Coronaviridae and the genus Alphacoronavirus, primarily affects piglets under 7 days old, causing symptoms such as diarrhea, vomiting, and dehydration. It has the potential to infect human primary and passaged cells in [...] Read more.
Swine acute diarrhea syndrome coronavirus (SADS-CoV), a member of the family Coronaviridae and the genus Alphacoronavirus, primarily affects piglets under 7 days old, causing symptoms such as diarrhea, vomiting, and dehydration. It has the potential to infect human primary and passaged cells in vitro, indicating a potential risk of zoonotic transmission. In this study, we successfully generated and purified six monoclonal antibodies (mAbs) specifically targeting the spike protein of SADS-CoV, whose epitope were demonstrated specificity to the S1A or S1B region by immunofluorescence assay and enzyme-linked immunosorbent assay. Three of these mAbs were capable of neutralizing SADS-CoV infection on HeLa-R19 and A549. Furthermore, we observed that SADS-CoV induced the agglutination of erythrocytes from both humans and rats, and the hemagglutination inhibition capacity and antigen–antibody binding capacity of the antibodies were assessed. Our study reveals that mAbs specifically targeting the S1A domain demonstrated notable efficacy in suppressing the hemagglutination phenomenon induced by SADS-CoV. This finding represents the first instance of narrowing down the protein region responsible for SADS-CoV-mediated hemagglutination to the S1A domain, and reveals that the cell attachment domains S1A and S1B are the main targets of neutralizing antibodies. Full article
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15 pages, 1250 KiB  
Article
Effect of SARS-CoV-2 Infection and BNT162b2 Vaccination on the mRNA Expression of Genes Associated with Angiogenesis
by Paulina Wigner-Jeziorska, Edyta Janik-Karpińska, Marta Niwald, Joanna Saluk and Elżbieta Miller
Int. J. Mol. Sci. 2023, 24(22), 16094; https://doi.org/10.3390/ijms242216094 - 8 Nov 2023
Viewed by 1054
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), discovered in December 2019 in Wuhan, China, caused the coronavirus disease 2019 (COVID-19). Due to the rate of spread of this virus, the World Health Organization, in March 2020, recognised COVID-19 as a worldwide pandemic. The [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), discovered in December 2019 in Wuhan, China, caused the coronavirus disease 2019 (COVID-19). Due to the rate of spread of this virus, the World Health Organization, in March 2020, recognised COVID-19 as a worldwide pandemic. The disease is multisystemic with varying degrees of severity. Unfortunately, despite intensive research, the molecular changes caused by SARS-CoV-2 remain unclear. Mechanisms affected by the virus infection include endothelial dysfunction and angiogenesis. Similarly, the vaccines developed so far affect the process of angiogenesis, contributing to the development of undesirable effects on part of the cardiovascular system. The presented research aimed to investigate the impact of the SARS-CoV-2 infection and the Pfizer Comirnaty vaccine (BNT162b2) on the molecular aspect of angiogenesis. We found that convalescents vaccinated with one dose of BNT162b2 were characterised by higher MMP-7 (metalloproteinases 7) expression than non-vaccinated convalescents and healthy volunteers vaccinated with one dose of BNT162b2. Moreover, non-vaccinated convalescents showed increased mRNA expression of ADAMTS1 (ADAM metallopeptidase with thrombospondin type 1 motif 1) compared to healthy volunteers vaccinated with one dose of BNT162b2. In addition, we showed significant sex differences in the expression of MMP-7. In conclusion, the results of our study suggest a significant impact of SARS-CoV-2 infection and vaccination on the course of angiogenesis at the molecular level. Full article
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20 pages, 4431 KiB  
Article
A Genetically Engineered Bivalent Vaccine Coexpressing a Molecular Adjuvant against Classical Swine Fever and Porcine Epidemic Diarrhea
by Hao Wang, Weicheng Yi, Huan Qin, Qin Wang, Rui Guo and Zishu Pan
Int. J. Mol. Sci. 2023, 24(15), 11954; https://doi.org/10.3390/ijms241511954 - 26 Jul 2023
Viewed by 1217
Abstract
Classical swine fever (CSF) and porcine epidemic diarrhea (PED) are highly contagious viral diseases that pose a significant threat to piglets and cause substantial economic losses in the global swine industry. Therefore, the development of a bivalent vaccine capable of targeting both CSF [...] Read more.
Classical swine fever (CSF) and porcine epidemic diarrhea (PED) are highly contagious viral diseases that pose a significant threat to piglets and cause substantial economic losses in the global swine industry. Therefore, the development of a bivalent vaccine capable of targeting both CSF and PED simultaneously is crucial. In this study, we genetically engineered a recombinant classical swine fever virus (rCSFV) expressing the antigenic domains of the porcine epidemic diarrhea virus (PEDV) based on the modified infectious cDNA clone of the vaccine strain C-strain. The S1N and COE domains of PEDV were inserted into C-strain cDNA clone harboring the mutated 136th residue of Npro and substituted 3′UTR to generate the recombinant chimeric virus vC/SM3′UTRN-S1NCOE. To improve the efficacy of the vaccine, we introduced the tissue plasminogen activator signal (tPAs) and CARD domain of the signaling molecule VISA into vC/SM3′UTRN-S1NCOE to obtain vC/SM3′UTRN-tPAsS1NCOE and vC/SM3′UTRN-CARD/tPAsS1NCOE, respectively. We characterized three vaccine candidates in vitro and investigated their immune responses in rabbits and pigs. The NproD136N mutant exhibited normal autoprotease activity and mitigated the inhibition of IFN-β induction. The introduction of tPAs and the CARD domain led to the secretory expression of the S1NCOE protein and upregulated IFN-β induction in infected cells. Immunization with recombinant CSFVs expressing secretory S1NCOE resulted in a significantly increased in PEDV-specific antibody production, and coexpression of the CARD domain of VISA upregulated the PEDV-specific IFN-γ level in the serum of vaccinated animals. Notably, vaccination with vC/SM3′UTRN-CARD/tPAsS1NCOE conferred protection against virulent CSFV and PEDV challenge in pigs. Collectively, these findings demonstrate that the engineered vC/SM3′UTRN-CARD/tPAsS1NCOE is a promising bivalent vaccine candidate against both CSFV and PEDV infections. Full article
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17 pages, 3803 KiB  
Article
Porcine Epidemic Diarrhea Virus and Its nsp14 Suppress ER Stress Induced GRP78
by Wei Zeng, Jingping Ren, Gan Yang, Changsheng Jiang, Ling Dong, Qi Sun, Yaofang Hu, Wentao Li and Qigai He
Int. J. Mol. Sci. 2023, 24(5), 4936; https://doi.org/10.3390/ijms24054936 - 3 Mar 2023
Cited by 2 | Viewed by 1848
Abstract
Porcine epidemic diarrhea virus (PEDV), a member of the α-coronavirus genus, can cause vomiting, diarrhea, and dehydration in piglets. Neonatal piglets infected with PEDV have a mortality rate as high as 100%. PEDV has caused substantial economic losses to the pork industry. Endoplasmic [...] Read more.
Porcine epidemic diarrhea virus (PEDV), a member of the α-coronavirus genus, can cause vomiting, diarrhea, and dehydration in piglets. Neonatal piglets infected with PEDV have a mortality rate as high as 100%. PEDV has caused substantial economic losses to the pork industry. Endoplasmic reticulum (ER) stress, which can alleviate the accumulation of unfolded or misfolded proteins in ER, involves in coronavirus infection. Previous studies have indicated that ER stress could inhibit the replication of human coronaviruses, and some human coronaviruses in turn could suppress ER stress-related factors. In this study, we demonstrated that PEDV could interact with ER stress. We determined that ER stress could potently inhibit the replication of GⅠ, GⅡ-a, and GⅡ-b PEDV strains. Moreover, we found that these PEDV strains can dampen the expression of the 78 kDa glucose-regulated protein (GRP78), an ER stress marker, while GRP78 overexpression showed antiviral activity against PEDV. Among different PEDV proteins, PEDV non-structural protein 14 (nsp14) was revealed to play an essential role in the inhibition of GRP78 by PEDV, and its guanine-N7-methyltransferase domain is necessary for this role. Further studies show that both PEDV and its nsp14 negatively regulated host translation, which could account for their inhibitory effects against GRP78. In addition, we found that PEDV nsp14 could inhibit the activity of GRP78 promotor, helping suppress GRP78 transcription. Our results reveal that PEDV possesses the potential to antagonize ER stress, and suggest that ER stress and PEDV nsp14 could be the targets for developing anti-PEDV drugs. Full article
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Review

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20 pages, 4152 KiB  
Review
Role of the MicroRNAs in the Pathogenic Mechanism of Painful Symptoms in Long COVID: Systematic Review
by Samuel Reyes-Long, Jose Luis Cortés-Altamirano, Cindy Bandala, Karina Avendaño-Ortiz, Herlinda Bonilla-Jaime, Antonio Bueno-Nava, Alberto Ávila-Luna, Pedro Sánchez-Aparicio, Denise Clavijo-Cornejo, Ana Lilia Dotor-LLerena, Elizabeth Cabrera-Ruiz and Alfonso Alfaro-Rodríguez
Int. J. Mol. Sci. 2023, 24(4), 3574; https://doi.org/10.3390/ijms24043574 - 10 Feb 2023
Cited by 4 | Viewed by 2559
Abstract
The ongoing pandemic of COVID-19 has caused more than 6.7 million tragic deaths, plus, a large percentage of people who survived it present a myriad of chronic symptoms that last for at least 6 months; this has been named as long COVID. Some [...] Read more.
The ongoing pandemic of COVID-19 has caused more than 6.7 million tragic deaths, plus, a large percentage of people who survived it present a myriad of chronic symptoms that last for at least 6 months; this has been named as long COVID. Some of the most prevalent are painful symptoms like headache, joint pain, migraine, neuropathic-like pain, fatigue and myalgia. MicroRNAs are small non-coding RNAs that regulate genes, and their involvement in several pathologies has been extensively shown. A deregulation of miRNAs has been observed in patients with COVID-19. The objective of the present systematic review was to show the prevalence of chronic pain-like symptoms of patients with long COVID and based on the expression of miRNAs in patients with COVID-19, and to present a proposal on how they may be involved in the pathogenic mechanisms of chronic pain-like symptoms. A systematic review was carried out in online databases for original articles published between March 2020 to April 2022; the systematic review followed the PRISMA guidelines, and it was registered in PROSPERO with registration number CRD42022318992. A total of 22 articles were included for the evaluation of miRNAs and 20 regarding long COVID; the overall prevalence of pain-like symptoms was around 10 to 87%, plus, the miRNAs that were commonly up and downregulated were miR-21-5p, miR-29a,b,c-3p miR-92a,b-3p, miR-92b-5p, miR-126-3p, miR-150-5p, miR-155-5p, miR-200a, c-3p, miR-320a,b,c,d,e-3p, and miR-451a. The molecular pathways that we hypothesized to be modulated by these miRNAs are the IL-6/STAT3 proinflammatory axis and the compromise of the blood–nerve barrier; these two mechanisms could be associated with the prevalence of fatigue and chronic pain in the long COVID population, plus they could be novel pharmacological targets in order to reduce and prevent these symptoms. Full article
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