ABSTRACT
Lactoferrin (Lf) is a dynamic and polyfunctional iron-binding protein found in mammalian milk. It possesses antiviral and antibacterial activities, as well as immunological qualities. Researchers have spent much time studying it, and it has lately received attention because of its link to the current coronavirus epidemic. Lf has been revealed to have antiviral properties against coronavirus. It shows that Lf can attach to several of the receptors utilized by coronaviruses, preventing them from entering the body. Other actions of Lf, host receptor angiotensin-converting enzyme-2 (ACE2), and the heparan sulfate proteoglycans (HSPGs), suggest that they may inhibit acute respiratory syndrome coronavirus (SARS-CoV) by binding to host cells. The U.S. Food and Drug Administration (FDA) has determined bovine lactoferrin (bLf) to be safe for human consumption. However, it is not a vitamin, and a study is underway to learn more about Lf’s additional advantages and if past discoveries of this molecule are worth examining. The coronavirus that causes acute respiratory syndrome might be prevented from adhering to host cells by Lf. HSPG and the host receptor ACE2 are significant in other research because Lf may inhibit the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from binding to host cells. Lf (enteric-coated Lf in particular, given its increased bioavailability) may have preventative and curative benefits in the continuing coronavirus disease-2019 (COVID-19) pandemic at some time.
ABSTRACT
Monitoring SARS-CoV-2 spread and evolution through genome sequencing is essential in handling the COVID-19 pandemic. The availability of patient hospital records is crucial for linking the genomic sequence information to virus function during the course of infections. Here, we sequenced 892 SARS-CoV-2 genomes collected from patients in Saudi Arabia from March to August 2020. From the assembled sequences, we estimate the SARS-CoV-2 effective population size and infection rate and outline the epidemiological dynamics of import and transmission events during this period in Saudi Arabia. We show that two consecutive mutations (R203K/G204R) in the SARS-CoV-2 nucleocapsid (N) protein are associated with higher viral loads in COVID-19 patients. Our comparative biochemical analysis reveals that the mutant N protein displays enhanced viral RNA binding and differential interaction with key host proteins. We found hyper-phosphorylation of the adjacent serine site (S206) in the mutant N protein by mass-spectrometry analysis. Furthermore, analysis of the host cell transcriptome suggests that the mutant N protein results in dysregulated interferon response genes. We provide crucial information in linking the R203K/G204R mutations in the N protein as a major modulator of host-virus interactions and increased viral load and underline the potential of the nucleocapsid protein as a drug target during infection.