Toll-like receptor (TLRs) agonists and antagonists for COVID-19 treatments.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) rapidly infects humans and animals which make coronavirus disease 2019 (COVID-19) a grievous epidemic worldwide which broke out in 2020. According to data analysis of the other coronavirus family, for instance severe acute respiratory syndrome SARS coronavirus (SARS-CoV), can provide experience for the mutation of SARS-CoV-2 and the prevention and treatment of COVID-19. Toll-like receptors (TLRs) as a pattern recognition receptor (PRRs), have an indispensable function in identifying the invader even activate the innate immune system. It is possible for organism to activate different TLR pathways which leads to secretion of proinflammatory cytokines such as Interleukin 1 (IL-1), Interleukin 6 (IL-6), Tumor necrosis factor α (TNFα) and type Ⅰ interferon. As a component of non-specific immunity, TLRs pathway may participate in the SARS-CoV-2 pathogenic processes, due to previous works have proved that TLRs are involved in the invasion and infection of SARS-CoV and MERS to varying degrees. Different TLR, such as TLR2, TLR4, TLR7, TLR8 and TLR9 probably have a double-sided in COVID-19 infection. Therefore, it is of great significance for a correctly acknowledging how TLR take part in the SARS-CoV-2 pathogenic processes, which will be the development of treatment and prevention strategies.

Potential therapeutic strategies for quercetin targeting critical pathological mechanisms associated with colon adenocarcinoma and COVID-19

Patients with colon adenocarcinoma (COAD) are at a higher probability of infection with COVID-19 than healthy individuals. However, there is no globally accepted treatment protocol for patients with COAD/COVID-19. Quercetin has been found to have significant antitumor, antiviral and anti-inflammatory effects in several studies. Therefore, this study sought to evaluate the potential of quercetin as the agent for COAD/COVID-19 and to explore its mechanisms. We used bioinformatics algorithms to obtain COAD/COVID-19-related genes (CCRG) from COAD-related transcriptome data and COVID-related transcriptome sequencing data, and used these genes to construct a COAD prognostic model. We intersected the CCRG with the therapeutic target genes of quercetin and obtained a total of 105 genes (potential target genes of quercetin for the treatment of COAD/COVID-19). By constructing a protein-protein interaction (PPI) network, we ascertained FOS, NFKB1, NFKB1A, JUNB, and JUN as possible core target genes of quercetin for the treatment of COAD/COVID-19. Bioinformatic analysis of these 105 genes revealed that the mechanisms for quercetin the treatment of COAD/COVID-19 may be associated with oxidative stress, apoptosis, anti-inflammatory, immune, anti-viral and multiple pathways containing IL-17, TNF, HIF-1. In this study, we constructed a prognostic model of COAD/COVID19 patients by using CCRG and elucidated for the first time the potential target genes and molecular mechanisms of quercetin for the treatment of COAD/COVID-19, which may benefit the clinical treatment of COAD/COVID-19 patients. However, no clinical trials have yet been conducted to further validate the findings, but this will be the future direction of our research.

Toll-like receptor (TLRs) agonists and antagonists for COVID-19 treatments

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) rapidly infects humans and animals which make coronavirus disease 2019 (COVID-19) a grievous epidemic worldwide which broke out in 2020. According to data analysis of the other coronavirus family, for instance severe acute respiratory syndrome SARS coronavirus (SARS-CoV), can provide experience for the mutation of SARS-CoV-2 and the prevention and treatment of COVID-19. Toll-like receptors (TLRs) as a pattern recognition receptor (PRRs), have an indispensable function in identifying the invader even activate the innate immune system. It is possible for organism to activate different TLR pathways which leads to secretion of proinflammatory cytokines such as Interleukin 1 (IL-1), Interleukin 6 (IL-6), Tumor necrosis factor α (TNFα) and type Ⅰ interferon. As a component of non-specific immunity, TLRs pathway may participate in the SARS-CoV-2 pathogenic processes, due to previous works have proved that TLRs are involved in the invasion and infection of SARS-CoV and MERS to varying degrees. Different TLR, such as TLR2, TLR4, TLR7, TLR8 and TLR9 probably have a double-sided in COVID-19 infection. Therefore, it is of great significance for a correctly acknowledging how TLR take part in the SARS-CoV-2 pathogenic processes, which will be the development of treatment and prevention strategies.

The Role of Oxidative Stress in Skeletal Muscle Myogenesis and Muscle Disease.

The contractile activity, high oxygen consumption and metabolic rate of skeletal muscle cause it to continuously produce moderate levels of oxidant species, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS). Under normal physiological conditions, there is a dynamic balance between the production and elimination of ROS/RNS. However, when the oxidation products exceed the antioxidant defense capacity, the body enters a state of oxidative stress. Myogenesis is an important process to maintain muscle homeostasis and the physiological function of skeletal muscle. Accumulating evidence suggests that oxidative stress plays a key role in myogenesis and skeletal muscle physiology and pathology. In this review, we summarize the sources of reactive oxygen species in skeletal muscle and the causes of oxidative stress and analyze the key role of oxidative stress in myogenesis. Then, we discuss the relationship between oxidative stress and muscle homeostasis and physiopathology. This work systematically summarizes the role of oxidative stress in myogenesis and muscle diseases and provides targets for subsequent antioxidant therapy and repair of inflammatory damage in noninflammatory muscle diseases.

Modulation of Innate Antiviral Immune Response by Porcine Enteric Coronavirus.

Host's innate immunity is the front-line defense against viral infections, but some viruses have evolved multiple strategies for evasion of antiviral innate immunity. The porcine enteric coronaviruses (PECs) consist of porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), transmissible gastroenteritis coronavirus (TGEV), and swine acute diarrhea syndrome-coronavirus (SADS-CoV), which cause lethal diarrhea in neonatal pigs and threaten the swine industry worldwide. PECs interact with host cells to inhibit and evade innate antiviral immune responses like other coronaviruses. Moreover, the immune escape of porcine enteric coronaviruses is the key pathogenic mechanism causing infection. Here, we review the most recent advances in the interactions between viral and host's factors, focusing on the mechanisms by which viral components antagonize interferon (IFN)-mediated innate antiviral immune responses, trying to shed light on new targets and strategies effective for controlling and eliminating porcine enteric coronaviruses.

Competitive Endogenous RNA Network Activates Host Immune Response in SARS-CoV-2-, panH1N1 (A/California/07/2009)-, and H7N9 (A/Shanghai/1/2013)-Infected Cells.

The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still ongoing, as is research on the molecular mechanisms underlying cellular infection by coronaviruses, with the hope of developing therapeutic agents against this pandemic. Other important respiratory viruses such as 2009 pandemic H1N1 and H7N9 avian influenza virus (AIV), influenza A viruses, are also responsible for a possible outbreak due to their respiratory susceptibility. However, the interaction of these viruses with host cells and the regulation of post-transcriptional genes remains unclear. In this study, we detected and analyzed the comparative transcriptome profiling of SARS-CoV-2, panH1N1 (A/California/07/2009), and H7N9 (A/Shanghai/1/2013) infected cells. The results showed that the commonly upregulated genes among the three groups were mainly involved in autophagy, pertussis, and tuberculosis, which indicated that autophagy plays an important role in viral pathogenicity. There are three groups of commonly downregulated genes involved in metabolic pathways. Notably, unlike panH1N1 and H7N9, SARS-CoV-2 infection can inhibit the m-TOR pathway and activate the p53 signaling pathway, which may be responsible for unique autophagy induction and cell apoptosis. Particularly, upregulated expression of IRF1 was found in SARS-CoV-2, panH1N1, and H7N9 infection. Further analysis showed SARS-CoV-2, panH1N1, and H7N9 infection-induced upregulation of lncRNA-34087.27 could serve as a competitive endogenous RNA to stabilize IRF1 mRNA by competitively binding with miR-302b-3p. This study provides new insights into the molecular mechanisms of influenza A virus and SARS-CoV-2 infection.

Susceptibility and Attenuated Transmissibility of SARS-CoV-2 in Domestic Cats.

Domestic cats, an important companion animal, can be infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This has aroused concern regarding the ability of domestic cats to spread the virus that causes coronavirus disease 2019. We systematically demonstrated the pathogenesis and transmissibility of SARS-CoV-2 in cats. Serial passaging of the virus between cats dramatically attenuated the viral transmissibility, likely owing to variations of the amino acids in the receptor-binding domain sites of angiotensin-converting enzyme 2 between humans and cats. These findings provide insight into the transmissibility of SARS-CoV-2 in cats and information for protecting the health of humans and cats.