Immunogenicity and protective potential of chimeric virus-like particles containing SARS-CoV-2 spike and H5N1 matrix 1 proteins.

Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has posed a constant threat to human beings and the world economy for more than two years. Vaccination is the first choice to control and prevent the pandemic. However, an effective SARS-CoV-2 vaccine against the virus infection is still needed. This study designed and prepared four kinds of virus-like particles (VLPs) using an insect expression system. Two constructs encoded wild-type SARS-CoV-2 spike (S) fused with or without H5N1 matrix 1 (M1) (S and SM). The other two constructs contained a codon-optimized spike gene and/or M1 gene (mS and mSM) based on protein expression, stability, and ADE avoidance. The results showed that the VLP-based vaccine could induce high SARS-CoV-2 specific antibodies in mice, including specific IgG, IgG1, and IgG2a. Moreover, the mSM group has the most robust ability to stimulate humoral immunity and cellular immunity than the other VLPs, suggesting the mSM is the best immunogen. Further studies showed that the mSM combined with Al/CpG adjuvant could stimulate animals to produce sustained high-level antibodies and establish an effective protective barrier to protect mice from challenges with mouse-adapted strain. The vaccine based on mSM and Al/CpG adjuvant is a promising candidate vaccine to prevent the COVID-19 pandemic.

Advances in Crosstalk between Porcine Circoviruses and Host.

Porcine circoviruses (PCVs), including PCV1 to PCV4, are non-enveloped DNA viruses with a diameter of about 20 nm, belonging to the genus Circovirus in the family Circoviridae. PCV2 is an important causative agent of porcine circovirus disease or porcine circovirus-associated disease (PCVD/PCVAD), which is highly prevalent in pigs and seriously affects the swine industry globally. Furthermore, PCV2 mainly causes subclinical symptoms and immunosuppression, and PCV3 and PCV4 were detected in healthy pigs, sick pigs, and other animals. Although the pathogenicity of PCV3 and PCV4 in the field is still controversial, the infection rates of PCV3 and PCV4 in pigs are increasing. Moreover, PCV3 and PCV4 rescued from infected clones were pathogenic in vivo. It is worth noting that the interaction between virus and host is crucial to the infection and pathogenicity of the virus. This review discusses the latest research progress on the molecular mechanism of PCVs-host interaction, which may provide a scientific basis for disease prevention and control.

Immunogenicity and protective potential of chimeric virus-like particles containing SARS-CoV-2 spike and H5N1 matrix 1 proteins

Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has posed a constant threat to human beings and the world economy for more than two years. Vaccination is the first choice to control and prevent the pandemic. However, an effective SARS-CoV-2 vaccine against the virus infection is still needed. This study designed and prepared four kinds of virus-like particles (VLPs) using an insect expression system. Two constructs encoded wild-type SARS-CoV-2 spike (S) fused with or without H5N1 matrix 1 (M1) (S and SM). The other two constructs contained a codon-optimized spike gene and/or M1 gene (mS and mSM) based on protein expression, stability, and ADE avoidance. The results showed that the VLP-based vaccine could induce high SARS-CoV-2 specific antibodies in mice, including specific IgG, IgG1, and IgG2a. Moreover, the mSM group has the most robust ability to stimulate humoral immunity and cellular immunity than the other VLPs, suggesting the mSM is the best immunogen. Further studies showed that the mSM combined with Al/CpG adjuvant could stimulate animals to produce sustained high-level antibodies and establish an effective protective barrier to protect mice from challenges with mouse-adapted strain. The vaccine based on mSM and Al/CpG adjuvant is a promising candidate vaccine to prevent the COVID-19 pandemic.

Differential Transcriptomics Analysis of IPEC-J2 Cells Single or Coinfected With Porcine Epidemic Diarrhea Virus and Transmissible Gastroenteritis Virus.

Porcine epidemic diarrhea (PED) and transmissible gastroenteritis (TGE) caused by porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) are two highly contagious intestinal diseases in the swine industry worldwide. Notably, coinfection of TGEV and PEDV is common in piglets with diarrhea-related diseases. In this study, intestinal porcine epithelial cells (IPEC-J2) were single or coinfected with PEDV and/or TGEV, followed by the comparison of differentially expressed genes (DEGs), especially interferon-stimulated genes (ISGs), between different groups via transcriptomics analysis and real-time qPCR. The antiviral activity of swine interferon-induced transmembrane protein 3 (sIFITM3) on PEDV and TGEV infection was also evaluated. The results showed that DEGs can be detected in the cells infected with PEDV, TGEV, and PEDV+TGEV at 12, 24, and 48 hpi, and the number of DEGs was the highest at 24 hpi. The DEGs are mainly annotated to the GO terms of protein binding, immune system process, organelle part, and intracellular organelle part. Furthermore, 90 ISGs were upregulated during PEDV or TGEV infection, 27 of which were associated with antiviral activity, including ISG15, OASL, IFITM1, and IFITM3. Furthermore, sIFITM3 can significantly inhibit PEDV and TGEV infection in porcine IPEC-J2 cells and/or monkey Vero cells. Besides, sIFITM3 can also inhibit vesicular stomatitis virus (VSV) replication in Vero cells. These results indicate that sIFITM3 has broad-spectrum antiviral activity.

Possible Targets of Pan-Coronavirus Antiviral Strategies for Emerging or Re-Emerging Coronaviruses.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which caused Coronaviruses Disease 2019 (COVID-19) and a worldwide pandemic, is the seventh human coronavirus that has been cross-transmitted from animals to humans. It can be predicted that with continuous contact between humans and animals, more viruses will spread from animals to humans. Therefore, it is imperative to develop universal coronavirus or pan-coronavirus vaccines or drugs against the next coronavirus pandemic. However, a suitable target is critical for developing pan-coronavirus antivirals against emerging or re-emerging coronaviruses. In this review, we discuss the latest progress of possible targets of pan-coronavirus antiviral strategies for emerging or re-emerging coronaviruses, including targets for pan-coronavirus inhibitors and vaccines, which will provide prospects for the current and future research and treatment of the disease.

Recent progress on the mutations of SARS-CoV-2 spike protein and suggestions for prevention and controlling of the pandemic.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection has caused a global pandemic in the past year, which poses continuing threat to human beings. To date, more than 3561 mutations in the viral spike protein were identified, including 2434 mutations that cause amino acid changes with 343 amino acids located in the viral receptor-binding domain (RBD). Among these mutations, the most representative ones are substitution mutations such as D614G, N501Y, Y453F, N439K/R, P681H, K417N/T, and E484K, and deletion mutations of ΔH69/V70 and Δ242-244, which confer the virus with enhanced infectivity, transmissibility, and resistance to neutralization. In this review, we discussed the recent findings of SARS-CoV-2 for highlighting mutations and variants on virus transmissibility and pathogenicity. Moreover, several suggestions for prevention and controlling the pandemic are also proposed.

Lactiplantibacillus plantarum as a Potential Adjuvant and Delivery System for the Development of SARS-CoV-2 Oral Vaccines.

The most important characteristics regarding the mucosal infection and immune responses against the Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) as well as the current vaccines against coronavirus disease 2019 (COVID-19) in development or use are revised to emphasize the opportunity for lactic acid bacteria (LAB)-based vaccines to offer a valid alternative in the fight against this disease. In addition, this article revises the knowledge on: (a) the cellular and molecular mechanisms involved in the improvement of mucosal antiviral defenses by beneficial Lactiplantibacillus plantarum strains, (b) the systems for the expression of heterologous proteins in L. plantarum and (c) the successful expressions of viral antigens in L. plantarum that were capable of inducing protective immune responses in the gut and the respiratory tract after their oral administration. The ability of L. plantarum to express viral antigens, including the spike protein of SARS-CoV-2 and its capacity to differentially modulate the innate and adaptive immune responses in both the intestinal and respiratory mucosa after its oral administration, indicates the potential of this LAB to be used in the development of a mucosal COVID-19 vaccine.

Necessary problems in re-emergence of COVID-19.

The ongoing pandemic of coronavirus disease 2019 poses a great threat to human beings. Although numerous patients have recovered, re-positive cases have been reported in several countries. Till now, we still know very little about the disease and its pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, more attention should be paid to the following aspects, such as post-discharge surveillance, asymptomatic infection, re-evaluation of influenza-like symptoms, and dynamic monitoring of genomic mutation of SARS-CoV-2.

Antiviral mechanisms of candidate chemical medicines and traditional Chinese medicines for SARS-CoV-2 infection.

The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global pandemic. Up to now, numerous medicines have been applied or approved for the prevention and control of the virus infection. However, the efficiency of each medicine or combination is completely different or still unknown. In this review, we discuss the types, characteristics, antiviral mechanisms, and shortcomings of recommended candidate medicines for SARS-CoV-2 infection, as well as perspectives of the drugs for the disease treatment, which may provide a theoretical basis for drug screening and application.

A recombinant Lactobacillus plantarum strain expressing the spike protein of SARS-CoV-2.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic in the past four months and causes respiratory disease in humans of almost all ages. Although several drugs have been announced to be partially effective treatments for this disease, no approved vaccine is available. Here, we described the construction of a recombinant Lactobacillus plantarum strain expressing the SARS-CoV-2 spike protein. The results showed that the spike gene with optimized codons could be efficiently expressed on the surface of recombinant L. plantarum and exhibited high antigenicity. The highest protein yield was obtained under the following conditions: cells were induced with 50 ng/mL SppIP at 37 °C for 6-10 h. The recombinant spike (S) protein was stable under normal conditions and at 50 °C, pH = 1.5, or a high salt concentration. Recombinant L. plantarum may provide a promising food-grade oral vaccine candidate against SARS-CoV-2 infection.

Recent progress on the diagnosis of 2019 Novel Coronavirus.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Therefore, convenient, timely and accurate detection of SARS-CoV-2 is urgently needed. Here, we review the types, characteristics and shortcomings of various detection methods, as well as perspectives for the SARS-CoV-2 diagnosis. Clinically, nucleic acid-based methods are sensitive but prone to false-positive. The antibody-based method has slightly lower sensitivity but higher accuracy. Therefore, it is suggested to combine the two methods to improve the detection accuracy of COVID-19.

Genetic evolution analysis of 2019 novel coronavirus and coronavirus from other species.

The Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a Public Health Emergency of International Concern. However, so far, there are still controversies about the source of the virus and its intermediate host. Here, we found the novel coronavirus was closely related to coronaviruses derived from five wild animals, including Paguma larvata, Paradoxurus hermaphroditus, Civet, Aselliscus stoliczkanus and Rhinolophus sinicus, and was in the same branch of the phylogenetic tree. However, genome and ORF1a homology show that the virus is not the same coronavirus as the coronavirus derived from these five animals, whereas the virus has the highest homology with Bat coronavirus isolate RaTG13.