Methods for modulation of coronavirus infection

A method to determine an efficacy of a compound to modulate the production of coronavirus neutralizing antibodies in a subject, comprising:

• obtaining a target cell, wherein the target cell is engineered to express an angiotensin-converting enzyme 2 receptor (ACE-2), a Transmembrane trypsin like serine protease (TMPRSS2), and a nicotinic acetylcholine receptor (nAChR);
• contacting the target cell with a viral particle comprising at least a portion of a coronavirus spike protein from the subject in the absence and the presence of:
• (i) a first sample obtained from the subject before treatment with the compound, and (ii) a second sample obtained from the subject after treatment with the compound, wherein the first and second samples comprise antibodies;
• and
• measuring levels of infection of the target cell in order to determine infectivity of the viral particles in the presence of the first subject sample and the second subject sample in order to determine a change in the activity or amount of neutralizing antibodies in the subject's first and second samples, wherein a change in the activity or amount of neutralizing antibodies is detected as a change in infectivity of the viral particles.

A method to identify a compound that can modulate coronavirus infection, comprising:

• (a) transfecting into a producer cell:
• i) a nucleic acid encoding a coronavirus spike protein or a portion thereof, and
• ii) a genomic viral expression vector comprising sequences from a virus that is not a coronavirus and that comprises an indicator nucleic acid that produces a detectable signal;
• (b) incubating the transfected producer cell under conditions such that pseudovirions that comprise the coronavirus spike protein or a portion thereof are generated;
• (c) contacting the pseudovirions of step (b) with a target cell under conditions such that the pseudovirions infect the target cell and in the presence or absence of the compound, wherein the target cell expresses an angiotensin-converting enzyme 2 receptor (ACE-2), a Transmembrane trypsin like serine protease (TMPRSSS2), and a nicotinic acetylcholine receptor (nAChR);
• and
• (d) measuring the amount of the detectable signal produced by the target cell in order to determine infectivity of the in the presence or absence of the compound.