ABSTRACT
COVID-19 global pandemics have called for researchers to design a suitable non-primate animal model as a tool for the study of pathogenesis, drug, and vaccine candidates. Studies using rodents have recently been developed and conducted to provide insights for various possible approaches to studying COVID-19. Here, we discussed the rodent model of COVID-19, primarily utilizing mice with strains of BALB/c and C57BL to understand the course of the and vaccine efficacy research. We searched for several online databases that studied the SARS-CoV-2 infection in rodents and vaccine development. We then appraised and discussed animal models to enhance drug development and vaccine studies on COVID-19. We appraised, discussed, and summarized 13 papers regarding the administration routes, observations, and indications for the study and further discussed the benefits and limitations of the studies. We found that researchers have successfully produced a transgenic animal model transfected with human ACE2 (hACE2), a good model of COVID-19 related high viral load with clinicopathology mimicking humans. We also found that the aged mice model presented a more serious disease than the less mature ones. Description and characterization of transgenic mice strains should also be applied to acquire a suitable animal model for COVID-19. Furthermore, SARS-CoV-2 has been shown to promote the number of pathogenic inflammation processes in BALB/c mice, which can be used for cytokines characterization, needed in drug and vaccine efficacy. © 2022 American Institute of Physics Inc.. All rights reserved.
ABSTRACT
BACKGROUND: Cytokine storm in COVID-19 patients has contributed to many morbidities and mortalities in patients. Studies have found that toll-like receptors (TLRs) and some Fc receptors play essential roles in the hyperactivation of the immune system. Up to date, researchers are still in progress to discover effective and safe drugs to alleviate the hyperinflammatory state in COVID-19. The previous studies had shown that Carthamus tinctorius and its bioactive compounds might have anti-inflammatory activities in animal models. AIM: We aimed to investigate the possible interactions of several flavonoids from C. tinctorius with several immune system components using a biocomputational approach. METHODS: Molecular docking was done using the AutoDock program based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) COVID-19 pathway. The most suitable receptors found were studied to study the interactions with several flavonoids from C. tinctorius. RESULTS: TLR4, TLR8, and FcγRIIa were found to bind with SARS CoV2 inflammatory pathway and further selected as macromolecules for potential interactions study with 22 flavonoids from C. tinctorius. Of the 22 flavonoids studied, daphnoretin showed the best binding affinity with TLR4 and Rutin was shown to attach best with FcγRIIa. Unlike its excellent binding to TLR4, daphnoretin showed weak binding to TLR8. CONCLUSION: Daphnoretin showed an excellent affinity with TLR4 and might be a good candidate as an inhibitor in hyperinflammatory reactions in COVID-19 DTLR8.
ABSTRACT
Objective: To discuss the potential and molecular mechanism of Carthamus tincorius derived hydroxysafflor yellow A (HSYA) as an alternative herbal adjuvant that may regulate various signaling pathways that might be related to the regulatory effects in COVID-19 patients with ALI and ARDS. Methods: We search Web of Science, PubMed, and Scopus using keywords: Carthamus tinctorius, adjuvant, cytokine storm, COVID-19, SARS-Cov-2, acute lung injury (ALI), and Acute Respiratory Distress Syndrome (ARDS), on 11 September 2020, and 18 December 2020. Results and Discussions: In COVID-19 patients, SARS-CoV-2 replication might be associated with hyper induction of pro-in-flammatory cytokine, which is known as a cytokine storm, and may cause acute lung injury (ALI) that leads to Acute Respiratory Distress Syndrome (ARDS). Carthamus tincorius derived HSYA were used in many studies, in vivo in animal models or in vitro in cell lines and showed inhibition of multiple inflammatory pathways that were involved in ALI and ARDS, which might occur in covid-19 patients. HSYA showed pleiotropic effects in regulating cytokine levels. It regulated TNF-α, IL-1β, IL-6, IFN-β, and showed protective effect by blocking TLR4, MyD88, TRIF, IRF3, NF-κB to avoid cytokine storm and prevent tissue damage. HSYA was showed to reduce oxidative stress-mediated damage, and down-regulate inflammatory cytokines. Further, it was relatively safe when studied as an adjuvant in HIV and cancer patients. Conclusion: We supposed that HSYA could be used as an alternative adjuvant in COVID-19 patients with ARDS. However, clinical trials are needed to prove its efficacy in COVID-19 patients with ARDS.