A cross‑institution collaboration compares SARS‑CoV‑2 and bat coronavirus RaTG13, revealing that a single amino acid change in OrfB9 can dramatically alter immune signaling in human versus bat lung cells.

Researchers identify OrfB9 as a potential molecular switch for spillover, showing that one amino acid alteration may influence cross‑species transmission from bats to humans.

In human lung cells, the SARS‑CoV‑2 version of OrfB9 dampens a key immune alarm, allowing viral replication, while in bat cells RaTG13’s OrfB9 activates immune proteins that suppress replication.

The findings point to a molecular signature that could serve as an early warning for spillover risk and deepen understanding of host adaptation, with implications for surveillance, vaccines, and antivirals.

The study appears in Cell Host & Microbe, published May 13, and details the collaborative effort.

The work underscores the co‑evolutionary arms race between viruses and hosts, showing how tiny genetic changes can reprogram immune responses and steer cross‑species transmission.

Published in Cell Host & Microbe on May 13, 2026, the research integrates molecular biology, immunology, virology, and computational biology to help predict and deter zoonotic events, with contributions from UCSF, Mount Sinai, Institut Pasteur, and Fred Hutch.

Researchers used the first laboratory‑grown greater horseshoe bat lung cell line to compare side‑by‑side, gaining native‑species insight into how the amino acid change affects immune pathways.

Overall, the work suggests that minimal genetic changes can determine spillover risk and that mapping protein interactions across species could serve as an early warning system for spillover threats.