FABP4 as a Therapeutic Host Target Controlling SARS-CoV2 Infection (preprint)

Host metabolic fitness is a critical determinant of infectious disease outcomes. In COVID-19, obesity and aging are major high-risk disease modifiers, although the underlying mechanism remains unknown. Here, we demonstrate that fatty acid binding protein 4 (FABP4), a critical regulator of metabolic dysfunction in these conditions, regulates SARS-CoV2 pathogenesis. Our study revealed that elevated FABP4 levels in COVID-19 patients strongly correlate with disease severity. In adipocytes and airway epithelial cells we found that loss of FABP4 function by genetic or pharmacological means impaired SARS-CoV2 replication and disrupted the formation of viral replication organelles. Furthermore, treatment of infected hamsters with FABP4 inhibitors alleviated lung damage and fibrosis and reduced lung viral titers. These results highlight a novel host factor critical for SARS-CoV2 infection and the therapeutic potential of FABP4-targeting agents in treating COVID-19 patients.

A Highly Potent SARS-CoV-2 Blocking Lectin Protein (preprint)

COVID-19 pandemic effected more than 180 million people around the globe causing more than four million deaths as of July 2021. Sars-CoV-2, the new coronavirus, has been identified as the primary cause of the infection. The number of vaccinated people is increasing however prophylactic drugs are highly demanded to ensure a secure social contact. There have been a number of drug molecules repurposed to fight against Sars-CoV-2, however the proofs for the effectiveness of these drug candidates is limited. Here we demonstrated griffithsin (GRFT), a lectin protein, to block the entry of the Sars-CoV2 into the Vero6 cell lines and IFNAR-/- mouse models by attaching to spike protein of the Sars-CoV-2. Given the current mutation frequency of the Sars-CoV-2 we believe that GRFT protein-based drugs will have a high impact in preventing the transmission both on Wuhan strain as well as any other emerging variants including delta variant causing high speed spread of COVID-19.

Neutralizing Antibody Response and Associated Factors in Coronavirus-19 Disease (COVID-19) up to One Month: A Case-Series of 129 Hospitalized Patients (preprint)

Purpose Little is known about the characteristics of neutralizing antibody(NAb) response in patients recovered COVID - 19. We aimed to elucidate the factors affecting presence and titers of in an early phase of infection up to 30 days.Methods A total of 129 laboratory-confirmed COVID-19 patients in a tertiary-care hospital were enrolled. Clinical and laboratory data were obtained retrospectively. SARS-CoV-2 specific NAb, IgM, and IgG antibody responses were analyzed. NAb-positive and negative patients were compared, to examine potential associations between clinical, demographical, and laboratory characteristics and the presence/titers of NAb.Results SARS-CoV-2 specific NAb, IgM and IgG were detected at the time of hospital discharge in 60.5%, 30.2%, and 51.9% of the patients, respectively. The presence of antibodies was 42.4%(NAb), 20.3%(IgM) and 44.1%(IgG) among patients within 5-9 days since onset; increased to 79.5%(NAb), 34.1%(IgM) and 47.7%(IgG) by 10-14 days; and detected in 66.7%(NAb), 50%(IgM), 83.3%(IgG) at/after day-15, following symptom onset. The median titer of neutralizing antibody(SN 50) was significantly higher in severe patients(25 versus 7.5, p= 0.009). Of the 23 severe patients, 52.2%(n=12) had higher NAb titers (i.e., SN 50 ≥ 1:25) when compared to that in non-severe patients(p= 0.021; OR = 2.89; 95%CI= 1.15 – 7.28), yet, potential effect of follow-up time on NAb status and titers could not be ruled out.Conclusion Presence and higher titers of NAb were detected more in severe patients compared to their non-severe counterparts. Survival analysis suggested that this difference could at least be partially explained by the length of follow-up after symptoms’ onset.