Mechanism: Easy Question, Not So Easy Answer

The last time I had to come up with a mechanism, it was on a (very tough) organic chemistry exam that I didn’t do very well on. Yet, whether it’s quantum mechanics or enzyme kinetics, asking how something works is one of the most fundamental questions in science.

Over the past couple of months, researchers have worked at remarkable speeds to figure out how the novel coronavirus (SARS-CoV-2) that has quarantined the world for 13+ months works. Particular attention has been paid to the all-too-familiar spike protein, which contains a particular region that can bind to a specific receptor (ACE2) on human cells. What makes this virus particularly infectious, however, is its ability to evade the immune system and pre-activate its spike proteins for cell membrane fusion. Thus, any effective treatment for SARS-CoV-2 would need to interfere with this process in which the virus can efficiently infiltrate human cells.

Griffithsin (abbreviated GRFT) is a red algae-derived protein that exhibits broad antiviral behavior against a wide variety of viruses, and scientists have most recently been interested in its ability to inhibit HIV cell entry. GRFT works by binding to various glycosylation sites (sugar scaffolding) present on all kinds of viral proteins, and has been shown to be effective against cousins of the current coronavirus, such as SARS-CoV and MERS. However, the detailed mechanism by which this protein inhibits coronavirus infection is not particularly well understood. This is especially true for SARS-CoV-2, a virus which remains every bit as mysterious as it is new.

Structural depiction of griffithsin (dimer form) (Xue et. al. 2012)

This summer, I’ll be figuring out how griffithsin blocks SARS-CoV-2 from entering cells, working to understand the complex interactions between GRFT and the coronavirus spike protein that allow for this unique behavior. Given my past history with figuring out mechanisms, it seems like a daunting task, but I have no doubt that I’ll learn a lot about experimental design along the way.

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