Table 2 A summary of host protective immune evasion strategies by SARS-CoV-2 and its variants

Defective recognition of SARS-CoV-2 by the host

Loss-of-function mutations in the immune sensor, the toll like receptor gene TLR7, encoding TLR7 which acts as the pattern recognition receptor (PRR) to recognize the pathogen-associated molecular pattern (PAMP). Thus the initial PAMP-PRR interaction

Martin-Sancho et al. (2021), van der Made et al. (2020), Wan et al. (2020)

Avoidance of innate immunity during viral entry

A defective interferon (IFN) response to SARS-CoV-2 by host that is resulted due to the impairment of expression of the IFN-stimulated genes (ISGs) encoding mainly LY6E, whose product stops the viral replication onward

Martin-Sancho et al. (2021), Kikkert (2020), Snijder et al. (2020)

Downregulation of several ISGs which specifically interferes the entry of SARS-CoV-2 spike (S) protein

Suppression of IFN-1 induced anti-viral state triggers hyper-inflammation and COVID-19 severity

Wan et al. (2020), Snijder et al. (2020)

Defective endosomal factors which are actually directed to inhibit the entry of SARS-CoV-2

Loss of control to inhibit SARS-CoV-2 replication

Loss of expression of the required RNA binding proteins which are supposed to hinder the viral RNA synthesis

Martin-Sancho et al. (2021), V'kovski et al. (2021)

Lack of production of the cluster of endoplasmic reticulum (ER)/Golgi-resident anti-viral ISGs which are dedicated to suppress the genes required for viral assembly

Curved membrane vesicles

Such modification of intracellular membranes makes the SARS-CoV-2 RNA replication easier

Klein et al. (2020)

Cap-snatching process

The host capping enzymes may be employed by SARS-CoV-2, resulting in viral mRNAs consisting of both the host capped small RNA (addition of a 7-methyl guanosine; and lacking of the 2′-O-methylation) and the virus-encoded RNA. Thus, the SARS-CoV-2 RNAs may escape recognition by the host innate immune RNA sensors

Beyer and Forero (2022), Mandilara et al. (2021), Kikkert (2020), Dai et al. (2020)

Avoidance of recognition by the melanoma differentiation-associated protein (MDA5) sensor

Avoid recognition by the MDA5 sensor which controls the innate immune response to SARS-CoV-2 in the lung epithelial cells. Viral endoribonuclease activity encoded in one of the non-structural genes may also hinder the recognition by MDA5 sensor

Yin et al. (2021), Kikkert (2020)

Evading host innate immunity by the viral endoribonuclease

Avoidance of the MDA5 recognition (as stated above)

Kikkert (2020), Drappier et al. (2015), Kindler et al. (2017)

Avoidance of the protein kinase R (PKR), and the 2’-5’ Oligoadenylate Synthetase (the OAS/RNAse L system, which triggers the IFN effector pathways for creating the anti-viral state in host. PKR and the OAS)/RNAse L system is involved in the recognition and destruction of foreign RNA. Thus, avoidance of this system hinders the elicitation of viral RNA sensing as well as the virus-eliminating mechanisms by innate immunity

Genetic mutations within SARS-CoV-2 spike (S) protein

Defective recognition or the inability of recognition of the receptor binding domain (RBD) of the viral spike (S) protein by the host angiotensin-converting enzyme 2 (ACE 2) receptor

Noor et al. (2022), Lazarevic et al. (2021), Korber et al. (2020), Zhang et al. (2020)