We missed SARS-CoV-2, what other coronaviruses are we ignoring?

After SARS-Cov came and went in 2003, we learned that bats in China harbor SARS-like coronaviruses with the capacity to infect human cells. This information was largely ignored, otherwise we would have stopped this pandemic in its tracks. A coronavirus that went from bats to pigs might represent yet another threat to human health.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) has caused outbreaks of lethal disease in piglets throughout China. This virus likely spilled over from Rhinolophus species bats into pigs in China. The swine industry in China is extensive and there are many opportunities for contact between humans and pigs, raising the question of whether SADS-CoV might infect humans.

To address this question, a variety of cells in culture were assessed for susceptibility and permissivity to SADS-CoV. Production of infectious virus was observed after infection of swine , primate, cat and human cell lines. Primary human lung cells, including microvascular endothelial cells , fibroblasts, human nasal epithelial, and human airway epithelial cells all produced infectious virus after exposure to SADS-CoV.

SADS-CoV is an alphacoronavirus, and is distantly related to human common cold coronaviruses HCoV-229E and HCoV-NL63. However, human sera to HCoV-NL63 did not block infection with SADS-CoV. The good news is that remdesivir, an antiviral drug that inhibits RNA synthesis, blocked replication of SADS-CoV.

Many cell receptors for CoV are known, including ACE2 for SARS-CoV and SARS-CoV2, DPP for MERS-CoV, and APN for HCoV-229E. Antibodies against these cell proteins do not block infection of cells with SADS-CoV, indicating that a different cell receptor is bound to initiate infection with this virus.

These observations indicate that SADS-CoV can infect primary cells from the human respiratory tract. Consequently, this virus should be considered a pandemic threat. What should be done to prevent another devastating pandemic such as the one caused by SARS-CoV-2? Without doubt, antiviral drugs that inhibit SADS-CoV (and a wide range of bat SARS-like CoV) should be identified. Remdesivir is a start but it can only be given intravenously, limiting its utility. Furthermore, humans who work in swine herds should be routinely screened for the presence of SADS-CoV-like viruses.

In the wake of the SARS-CoV-2 pandemic, we can no longer ignore the threats to humanity posed by CoV and other viruses that circulate in bats, rodents, and other non-human animals. We could have prevented the SARS-CoV-2 pandemic with the scientific knowledge obtained before 2019. Have we learned a lesson for the next pandemic?