COVID-19 Variant Supplement - Understand the high pathogenicity and zoonotic transmission of the COVID-19 virus: evasion of host innate immune responses

Coronaviruses are not new to humans. The human coronaviruses OC43 and 229E were discovered as early as in the 1960s. Both viruses cause common cold, a mild infection of our upper respiratory tract. However, the story started to change in 2002 when SARS broke out in China and other countries. This outbreak was caused by a new coronavirus which originally came from bats. Most importantly, this SARS coronavirus is highly pathogenic, with a fatality as high as 10%. Ten years later, a more deadly coronavirus caused the MERS outbreak. Now, a new coronavirus came back, is raging in China, may cause a global pandemic if not controlled. This new virus, COVID-19 (or SARS-CoV-2), has infected more and killed more than the total number by both SARS and MERS. Two urgent questions need to be addressed. How did these coronaviruses transmit from animals into humans? What have made them so pathogenic and lethal? Humans are protected from viral diseases by the immune system. These pathogenic coronaviruses must have found ways to evade the immune responses so that they can spread in humans and cause fatal illness. We thus propose this research to elucidate how this COVID-19 virus does this. The findings will identify the key viral genes that suppress immune responses by blocking essential signaling pathways. Our results will open new avenues for the development of effective interventions to halt the COVID-19 break.