We are leading or assisting on several SARS-CoV-2 projects, as a matter of urgency, as follows
1. SARS-CoV-2 virus facility. The group listed at 3, below, have concluded that the sensible facility for regular virology is the Dunn School CL3 suite, freeing up capacity for more immunologically-focussed and clinical SARS-CoV-2 work at the PMB and WIMM facilities.
a. Samples. Clinical colleagues are storing positive patient samples for us until we are cleared to receive them and grow them up.
b. Service provision for others. In conjunction with the lab of Quentin Sattentau, we will be providing our affiliates with basic virus culture, RNA extraction, plaque and TCID50 titration assays using the US-CDC and the WHO-recognized protocols from Malik Pieris and Leo Poon, both Dunn School graduates, currently at Hong Kong.
c. Our experiments. We will be exploiting the hiPSC-differentiation platforms established in our lab to generate tissue-type macrophages and also airway epithelia in mono- and co-culture to study
i. (with Tao Dong, WIMM, and Malik Pieris, HKU) investigating polymorphic SNPs associated with altered Covid19 susceptibility though gene editing isogenic pairs in well-characterized human genomes.
ii. (with Malik and Leo) Investigating macrophage and epithelial infection under near physiological conditions, and in the presence of antibody, complement and inflammatory mediators
iii. (with Ebrahimi, Chemistry, and pharma partners) Phenocopying the RSAD2 (Viperin)-induced “hostile metabolic environment” in MPh using targeted nucleoside analogues and novel designer molecules
iv. (with SomaLogic, Boulder, CO) testing their anti-SARS Spike glycoprotein Somamers (slow off-rate aptamers) for neutralizing potency, for potential therapeutic purposes.
2. Lenti(S) pseudotype facility (CL2, OMPI2). We will use the optimized S-expression system developed at HKU to make pseudotypes of SARS-Cov-2 on a standard lentivirus reporter background (pNL4.3.ΔE.iGFP). This will provide us and our collaborators with much faster screens of entry inhibitors, receptor tropism variants, neutralizing antibodies, etc.
3. Local Affiliates.
i. Nicole Zitzmann (multi-centre drug tests)
ii. Alfredo Castelo-Palomares (RNP formation in infected cells)
i. Paul Klenerman (serology and MAIT cells)
ii. Peter Simmonds (sub-genomic replicons)
i. Jan Rehwinkel (innate cellular resistance)
ii. Tao Dong (polymorphisms in host IFN-response genes)
i. William S. James (antibody-mediated enhancement, alternate macrophage receptors, RSAD2 mimetics, screening neutralizing aptamers. Rapid diagnostics)
ii. Quentin Sattentau (cell tropism, antibody neutralization)
iii. Ervin Fodor (replicase inhibitors)
iv. Sumana Sanyal (cellular proteases and inhibitors in virus assembly/maturation, nanobodies for neutralization)
v. Ivan Ahel (antiviral ADP ribosylases)