Flaviviruses In Vitro

Flaviviruses are a major family of pathogens and cause dangerous arthropod-borne diseases such as dengue fever (DENV), Japanese encephalitis (JEV), yellow fever (YFV), zika (ZIKV) and others.

DENV infects more than 50 million people worldwide every year, causing a range of clinical syndromes from mild febrile illness to Dengue hemorrhagic fever/shock syndrome (DHF/DSS). Development of effective vaccines and therapeutics against DENV is becoming a high priority for governments and the pharmaceutical industry.

Japanese encephalitis results in high fevers and can damage the nervous system. Yellow fever is endemic in tropical regions and has a high mortality rate.

In vitro screens such as cytopathic effect (CPE), neutralization, and yield-reduction assays are used to test the activity of candidate compounds against flaviviruses. Typically, Vero cells are used for these cell-based assays. Other cell lines can be evaluated upon request.

  • Vero cells infected and viral plaques detected using a standard immunoplaque assay

  • K562 cell infected and percentage of DENV-positive cells analyzed by flow cytometry
Fig. 1 Survival after challenge with INFV H1N1 A/Pert/261/2009 (Tamiflu-resistant strain). Inoculum 1xLD90=1.0E+05 PFU/mouse
Survival after challenge with INFV H1N1 A/Pert/261/2009 (Tamiflu-resistant strain) 1.0E+05 PFU/mouse
Survival and weight change in BALB/c mice challenged with INFV A/ Texas/36/91 (H1N1) and treated with antiviral Osletamivir Phosphate (Tamiflu)
Lung viral load and Survival (30 % weight loss cut-off) in BALB/c mice challenged with INFV H3N2 A/HK/1/68.

Alpha (UK) – B. 1.1.7 / 501Y.V1

amino acid mutations: del69–70 HV, del144 Y, N501Y, A570D, D614G, P681H, T761I, S982A, D1118H

Beta (South Africa) – B.1.351

amino acid mutations: K417N, E484K, N501Y, D614G, A701V

Gamma (Brazil) – P.1

amino acid mutations: L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I

Epsilon (Ca, USA) B.1.427

amino acid mutations: L452R, D614G

SARS-CoV-2 Parental Strain Wild Type (Wuhan)
SARS-CoV-2 D614G Variant

amino acid mutations: D614G

Epsilon (Ca, USA) B.1.429

amino acid mutations: S13I, W152C, L452R, D614G

SARS-CoV-2 Delta Variant

amino acid mutations: L452R, E484Q