RT Journal Article
SR Electronic
T1 Inhibiting the reproduction of SARS-CoV-2 through perturbations in human lung cell metabolic network
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000869
DO 10.26508/lsa.202000869
VO 4
IS 1
A1 Hadrien Delattre
A1 Kalesh Sasidharan
A1 Orkun S Soyer
YR 2021
UL https://www.life-science-alliance.org/content/4/1/e202000869.abstract
AB Viruses rely on their host for reproduction. Here, we made use of genomic and structural information to create a biomass function capturing the amino and nucleic acid requirements of SARS-CoV-2. Incorporating this biomass function into a stoichiometric metabolic model of the human lung cell and applying metabolic flux balance analysis, we identified host-based metabolic perturbations inhibiting SARS-CoV-2 reproduction. Our results highlight reactions in the central metabolism, as well as amino acid and nucleotide biosynthesis pathways. By incorporating host cellular maintenance into the model based on available protein expression data from human lung cells, we find that only few of these metabolic perturbations are able to selectively inhibit virus reproduction. Some of the catalysing enzymes of such reactions have demonstrated interactions with existing drugs, which can be used for experimental testing of the presented predictions using gene knockouts and RNA interference techniques. In summary, the developed computational approach offers a platform for rapid, experimentally testable generation of drug predictions against existing and emerging viruses based on their biomass requirements.