SARS-CoV-2 and DC-SIGN: The Overlooked Path

I discovered my love for science when I was asked to be a pilot student for lessons at the Fairbanks STEM Lab in Vermont. I quickly learned that my previous assumptions about the subject were all wrong, after poring over petri dishes and studying the anatomy of Caenorhabditis elegans. Shortly after, I was introduced to the New Hampshire Academy of Science: since the long hours spent conducting independent research, surrounded by equally passionate peers, I haven’t looked back. I didn’t think it could become any better until my research granted me the qualifications to become inducted into the AJAS. I am so honored to have the opportunity to become a part of this community for a third consecutive year.

My research this year was inspired by my findings in research I conducted in 2020: A Computational Analysis of SARS Coronavirus 2 Spike Glycoprotein Binding To ACE2 and DC-SIGN. The study suggested that DC-SIGN may bind more strongly to the virus than ACE2 does. Since so many variants have evolved, and they can have such dire consequences on public health, I wanted to expand the study to observe the potential binding between the variants and DC-SIGN. Most research regarding SARS-CoV-2 involves binding to the ACE2 receptor to invade the body. However, SARS-CoV-2 could be binding to other receptors as well, potentially expanding treatment options if explored. With my research this year, I want to further bridge the information gap and provide more data on the functions of SARS-CoV-2 so we can overcome and recover from the COVID-19 pandemic.

In Silico Analysis of Initial Binding Interactions of DC-SIGN and SARS-CoV-2 VOCs

Since its appearance in 2019, multiple variants of SARS-CoV-2 have emerged. The World Health Organization (WHO) classifies variants based on their levels of potential harm. Variants of Concern (VOCs) is a classification that indicates potential for increased transmissibility, increased virulence, and reduced effectiveness to preventative measures or treatments. The VOCs investigated in this study were Alpha, Beta, and Gamma. Published research suggests that SARS-CoV-2 and its variants bind with angiotensin-converting enzyme 2 (ACE2). SARS-CoV-2 may also bind to the dendritic cell-specific intercellular adhesion molecule grabbing non-integrin (DC-SIGN). This dendritic cell receptor, after recognizing and binding to a variety of pathogens, including coronaviruses, enables binding between dendritic cells and T-lymphocytes. This study worked to extend the knowledge of the COVID-19 disease process through conducting in silico analyses of the initial binding interactions of DC-SIGN and the SARS-CoV-2 spike proteins of Alpha, Beta, and Gamma variants, at increasing temperatures. This was intended to mimic a fever in humans. The collected data included: dissociation constants, Gibbs free energy, and interfacial contact points of DC-SIGN bound to the Alpha, Beta, and Gamma spike protein variants. The results suggest that the initial binding interactions were strongest between DC-SIGN and wild-type SARS-CoV-2, followed by the variants Beta, Gamma, and lastly Alpha. The Gibbs free energy values for Beta, Gamma, and Alpha, respectively, were -14.1, -13.1, 10.9, and -10.1 kcal/mol. Following the same order, the dissociation constants of their interactions at 25℃ were 0.049, 0.26, 11, and 42 nM. When modeled at 37℃, the values were 0.12, 0.6, 22, and 81 nM. At 40℃ the values were 0.15, 0.74, 26, and 95 nM. These data indicate that as temperature increases, the dissociation constant increases between DC-SIGN and the Alpha, Beta, and Gamma variants. This suggests that fevers decrease the binding affinity between DC-SIGN and VOCs. The number of interfacial residues involved in the binding between DC-SIGN and the variants is consistent with this data. This study provides further evidence that there are additional host-virus interactions beyond ACE2 that should be studied to provide insights on the function of SARS-CoV-2 and the development of treatments.

To view more details of this research, please feel free to download the attached file to access the complete scientific paper of "In Silico Analysis of DC-SIGN Binding to SARS-CoV-2 Variants of Concern".