**6. The effect of circadian rhythm on SARS-CoV-2-infection and host immune response**

Many physiological processes influenced by 24-hour circadian rhythms has been known within individual cells. Even virology and circadian rhythms seem like different fields of biology, studies have suggested a novel interaction between viral infection and the circadian clock [45]. Edgar et al. showed 10 times higher viral replication in the mice infected at the start of their resting phase, likely as late evening for humans [45]. The finding confirmed the relationship between the circadian phase and virus infection. This data shows viral infection can directly affect the advantage of physiological rhythms in combating viruses. Noteworthy, a new study also indicated that the expression of the genes exhibited circadian rhythm in monocytes are shifting between two-time points showing the active and the resting periods in human individuals, which also indirectly affects SARS-CoV-2 replication [46]. The drug intake should also be adjusted considering the circadian rhythm of the body and virus to increase the efficacious of inhibitory compounds (**Figure 3**).

Another study also shows circadian clock has a central role in coordinating daily physiological processes involving immunity and biological process that humans are more susceptible to infections at certain times of the day cause of the function related to defense systems (**Figure 3**) with a daily rhythmic pattern [47]. In viral diseases, deciphering the complex relationships between circadian timekeeping, host immunity, and host-virus interactions has a great potential to unravel the complexity of severe acute respiratory syndrome coronavirus pathogenicity. Infection severity which may be regulated by the circadian clock affecting therapy positively against the novel pathogen may also result in recession of the pathogen. Therefore, circadian nature accounted for responses needs urgent studies on clock–infection biology in SARS-CoV-2. Even the pathophysiology of SARS-CoV-2 infection and its severe complications are not well understood, SARS-CoV-2 severity may also depend on day-night cycle (**Figure 3**). The battle between virus replication and its neutralization by the host immune system could move simultaneously with the circadian activity phase of the host. Accelerating the activity of circadian immunity factors may help to control virus replication, as circadian clocks provide a competitive advantage to the host against SARS-CoV-2.

*Utilization from Computational Methods and Omics Data for Antiviral Drug Discovery… DOI: http://dx.doi.org/10.5772/intechopen.98319*

#### **Figure 3.**

*Cellular clock affects the virus life cycle (1) which directly/ indirectly influenced by circadian clock of the host cell. These cases trigger multiple steps in regulation of different pathways (2) against virus and its replication phases involving particle genesis. In addition, immune responses combating viral infections regulated by circadian clocks could change depending on day and night (3). Illustration was created with BioRender.com by the authors of this chapter.*

As known defect on the circadian clock in hosts causes increasing of pathogen replication and invasion, which indicates that the severity of infection influenced by circadian rhythms. All these cases can be followed by omics technologies comprising genomics, transcriptomics and proteomics data [48, 49]. We stress the combination of the whole omics data to understand all biological cases related to SARS-CoV-2 and host defense mechanism. In consequence, exact treatment times aiming to control of virus will provide higher success in managing the disease. Circadian Expression Profiles Database (CircaDB) (http://circadb.hogeneschlab. org/) could be beneficial for the evaluation of omics data with expression profiles related to the circadian clock [50]. Notably, the expression profiles of potential drug targets considering the circadian rhythm of the host could provide a new strategy for effective compounds depending on application doses, which may affect the efficiency of tested pre-purposed or novel compounds. We need to better understand how the circadian clock affects SARS-CoV-2 infection to optimal clinical management of the virus.

Another highlighted point for drawing the attention of the scientists, virulent agents causing infections could help to shape our genome that is also responsible for various polymorphic structure involving many loci related to MHC antigen processing [51]. There is also strong evidence on the effect of the virus infection depending on HLA allele's expression [52], even their influence is moderate level. Accordingly, the resistance to pathogens comprising viruses conferred by several genes acts at different stages of the host-pathogen interaction. The finding on another virus HIV at least 250 genes affecting the success of the infection has been demonstrated [53]. Consequently, the lack of genes or its impairment could have a negative or less effect on the virus invasion. These cases arise from deficient genes which lead to increased susceptibility to different virus infections [54].
