Figure 3.

Possible connection between the pathophysiology of cancer and SARS-CoV-2 infection. SARS-CoV-2 virus entry into the host cell is facilitated by spike protein binding to ACE and activation by TMPRSS2. After binding, viral particles undergo endocytosis and active PAK1. Moreover, due to the upregulation of cytokine levels (IL-6, IL-1, and IL-8), JAK/STAT pathway, and TLRs, gets activated, which will further activate the TIR-domain-containing adapter-inducing interferon-β family (TRIF). Following this, TRIF recruits TNF receptor-associated factor (TRAF) which is followed by activation of the inflammatory marker, NF-κB, present in the cytosol. This is followed by nuclear translocation of NF-κB and binding with DNA, and ultimately the formation of CCL2 protein, results in fibrosis. The phenomenon is termed as cytokine storm and is responsible for multiorgan failure and death in cancer patients with COVID-19. Toclizumab, a monoclonal antibody, and situximab, a chimeric mouse–human monoclonal antibody, were both used to block the IL-6 receptor and already exhibited antitumor efficacy under diverse randomized trials control trials for further assessment of its effectiveness for COVID-19 patients. Another drug, propolis, was used to treat lung fibrosis during COVID-19 infection of cancer patients. Propolis inhibits the PAK1 activation in lung fibrosis by stimulating CCL2 production. PAK1 blockers may help in reviving the immune system, preventing lung fibrosis caused by viruses. In this context, propolis, a PAK1 inhibitor, was explored as a therapeutic strategy for COVID-19 patients.