Scientists studying the molecular underpinnings of COVID-19 have bad news to share: in addition to the dangerous omicron variant, the upcoming winter season is going to worsen the pandemic. That’s because there’s more evidence than ever that COVID-19 is a seasonal disease.
A new analysis by University of Illinois’ Gustavo Caetano-Anollés demonstrates these seasonal mutation patterns, and even identifies a molecular culprit behind COVID-19 seasonality. This discovery, however, came from a rather unexpected place—coral reefs.
In 2019, scientists in China found that a type of lectin—galectin—was involved in recognition between photosynthetic dinoflagellates and coral polyps. But this recognition mechanism didn’t work as well when water temperatures fell outside a narrow thermal band: 25-30˚C. It was a first hint that galectins sense external temperatures, and an explanation for coral bleaching.
Applying this discovery to their own line of research, Caetano-Anollés and his team analyzed tens of thousands of SARS-CoV-2 genomes, eventually discovering a galectin-like structure on the spike protein. The researchers think galectin protein structures sense external conditions and, when it’s not too hot or humid, trigger a conformational change in the spike protein of the virus, allowing viral RNA to enter host cells.
“Think of the spike as a little jar that has flaps on top to keep it closed. When temperature is high, the jar stays completely closed and cannot spill its infectious contents. But when its flaps recognize the host cell in the lung—under cool and dry conditions—the jar opens, releasing a fusion peptide that helps merge the virus and host membranes. This allows the virus to enter the cell and make more of its kind,” explained Caetano-Anollés, a professor of bioinformatics.
As he and his team learned more about galectin protein structures, they discovered the region is more than just a breeding ground for virus spread: it also facilitates mutations.
“Remarkably, we find the galectin-like structure is a frequent target of mutations because it helps the virus evade or modulate the physiological responses of the host to further its spread and survival,” said Caetano-Anollés.
Tracking mutations in the galectin protein region led the researchers to identify a seasonal pattern across the globe. Focusing on genomic changes worldwide, they found bursts of rapid mutation occurring throughout 2020, often leading to new variants of concern. The bursts were only firing in parts of the globe experiencing winter or in high elevation locations where weather remains cool year-round.
“These bursts are responsible for the rise of the Delta variant and new viral variants in the making,” said Caetano-Anollés.
Significantly, the researchers found that the seasonal bursts were occurring in the N-terminal region of the spike protein—where the galectin structure is located—providing more evidence of its role in the spread of the virus.
Caetano-Anollés’ laboratory is now exploring the millions of viral sequences acquired worldwide to determine how genomic makeup is changing the behavior of SARS-CoV-2. If they can further unravel the molecular underpinnings of COVID-19’s seasonality, Caetano-Anollés says it could predict future mutations and potentially pave the way for new therapeutics or vaccines.
“Understanding how these processes of viral diversification occur is crucial for mitigations,” he concluded.