The many referenced sources indicate the modulation of key cell-signaling pathways were effective in controlling the SARS-CoV infection. The same are as follows:
1- Targeting coronaviral replication and cellular JAK2 mediated dominant NF-κB activation for comprehensive and ultimate inhibition of coronaviral activity. Sci Rep 2017;7:1–13. doi:10.1038/s41598-017-04203-9.
2- Severe acute respiratory syndrome Coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3‐dependent ubiquitination of ASC. FASEB J 2019;33(8):8865–8877. doi:10.1096/ fsb2.v33.810.1096/fj.201802418R.
3-Inhibition of NF- kB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J Virol 2014;88:913–924. doi:10.1128/jvi.02576-13.
In reference to these published work, one may perform the experimental work using the strategies recently published in Medical Hypotheses Journal entitled " Serum albumin-mediated strategy for the effective targeting of SARS-CoV-2".
Some articles have been reported pointing out that inhibiting the pro-inflammatory cytokine signalling pathways could be a very promising path. However, in my understanding, JAK or STAT3 inhibitors may not be as selective and interfere with the classic signalling of IL-6 (anti-inflammatory activity). However, antagonists of the trans-signalling of the soluble form of the interleukin sIL-6R, such as the monoclonal antibody Tocilizumab, have high selectivity in modulating only the trans-signalling. Currently, some isolated and non-randomized clinical tests have been published, indicating a great potential for the remission of symptoms of COVID-19.
Non-randomized clinical tests with Tocilizumab:
[1] https://doi.org/10.1002/jmv.25801
[2] https://doi.org/10.1016/j.annonc.2020.03.300
[3] https://doi.org/10.1182/bloodadvances.2020001907
Mechanism of pharmacological action of Tocilizumab:
[4] https://doi.org/10.1186/s12967-020-02339-3
[5] https://doi.org/10.1101/2020.04.08.029769
[6] https://doi.org/10.1038/ni.3153
[7] https://doi.org/10.1038/nrclinonc.2018.8
Do you mean baricitinib (Olumiant),tofacitinib (Xeljanz), and upadacitinib (Rinvoq), are approved by the FDA to treat rheumatoid arthritis... Blood clots in the veins of your legs (deep vein thrombosis, DVT) or lungs (pulmonary embolism, PE) can happen in some people taking OLUMIANT.
Or
ruxolitinib... That enganches viral therapy un lung 10.1038/s41417-018-0074-6...
Dear All,
Thank you for your responses, although I completely agree with the use of the Anti-IL-6R antibody in critically ill patients however what if the switch causing further production and triggering of the IL-6 turned off in the early phase of an infected person. In a simple word, if the drug/classical molecule delivered to virus-infected cells where it modulates the signaling network in such a way that leads to fast apoptosis and disposal of infected cells only, it will lead to less immune response and multiplication of virus in the infected person.
Please see this paper for the plan of maximum delivery of the drug to infected cells “Serum albumin-mediated strategy for the effective targeting of SARS-CoV-2”.
Best regards,
Pushpendra
Follow, these articles
Non-randomized clinical tests with Tocilizumab:
[1] https://doi.org/10.1002/jmv.25801
[2] https://doi.org/10.1016/j.annonc.2020.03.300
[3] https://doi.org/10.1182/bloodadvances.2020001907
Thank you all for your responses and for participating in this discussion. the given link has summarized each aspect of the discussion thoroughly.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105343/pdf/can-14-1022.pdf
Thanks and Regards
Pushpendra