Developing viral vaccines and antiviral drugs is extremely challenging. Viruses are so complex – researchers first need to solve the virus structure and understand its life cycle. This knowledge is what enables the foundation of effective vaccines and the search for drugs that can inhibit or block a crucial step in the virus’ life cycle. Are you being challenged by a virus’ complexity? Learn how NanoTemper tools help your research.
Virus structure and function
Knowing what a virus is made of — nucleic acid, protein capsid, and for some a lipid envelope — is just half of the story. Researchers still need to figure out how these components are arranged — i.e. looking at crystals using electron microscopy — and what role they play in the virus life cycle often by characterizing interactions with host cell proteins and nucleic acids.
Get clues for drug development from the structure and function of MERS-CoV Nsp15
Nsp15 plays an essential role in the life cycle of coronavirus (CoV). But the structural information of this protein from MERS-CoV is missing. To shed light on its structure and functionality, this study looked at the complex formation between Nsp15 and other non-structural viral proteins. MST was used to confirm that Nsp15 associates to Nsp8 and Nsp8/Nsp7 with low micromolar affinities, and looked at how this association might affect catalytic activity. Learn more
Study dimerization of CoV nsp9 and its effect on nucleic acid binding affinity
Nsp9 is an important RNA binding subunit in the RNA-synthesizing machinery of all CoV. Understanding the mechanism of nsp9 dimerization and nucleic acid binding provides new insight for antiviral drug development. The authors used MST to get the binding affinity (Kd) of nsp9 with various mutations and their effects in dimerization and binding to ssDNA – while EMSA could only confirm binding but not measure the affinity. Learn more
Help resolve the spike glycoprotein structure with cryo-EM
The entry of CoV into cells is mediated by the transmembrane spike glycoprotein S, which forms a trimer and has receptor-binding and membrane fusion functions. Understanding the structure of this glycoprotein pre- and post-fusion can help in the design of vaccines. MST revealed that the binding affinity between glycoprotein S from mouse hepatitis virus and the soluble mouse receptor was in the nanomolar range. Learn more
Virus life cycle
In order to produce copies of itself, a virus must follow a multi-step process. It starts with the attachment to a receptor on the host cell membrane and ends with the release of the virus progeny. One way researchers continue to characterize each step, is by looking at how the proteins involved in this process interact with one another.
Block Influenza A virus entry with a multivalent inhibitor
Influenza A virus spike protein hemagglutinin binds to sialic acid on the cell membrane in a multivalent way. Designing multivalent binders is a promising approach to prevent infection. This study presents a multivalent binder that is shown to inhibit virus infection in vitro, ex vivo, and in vivo. MST is used to validate the optimal construction of the inhibitor measuring its interactions with Influenza A virus. Learn more
Reveal what makes protection against HIV-1 infection species-specific
Cellular protein TRIM5α gives resistance to HIV-1 in rhesus monkeys, but not in humans. It binds to the virus protein shell despite the high mutation rate seen in many retroviruses. This study sought to find out what virus capsid arrangements were responsible for the species-specific resistance. MST measurements revealed that the HIV-1 capsid surface is critical for the binding of TRIM5α and its species-specific protection against infection in rhesus monkeys. Learn more
In the past decade, my research has focused on characterizing multivalent binders against the spike proteins of the influenza A virus. MST made it possible to determine binding constants using whole virus particles, which revealed important insights on multivalent binders interacting with the native virus surface.
I highly recommend this valuable technology for virus binding studies.
Dr. Daniel Lauster