Replies

From text of article you cited...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097181/

“Alternatively, endocytosis can also be suppressed by a high pH. Chloroquine is an anti-malarial drug that sequesters protons into lysosomes to increase the intracellular pH. It has broad-spectrum antiviral activities against numerous CoVs (SARS-CoV, MERS-CoV, HCoV-229E and HCoV-OC43) and other RNA viruses in vitro123,210,211,212,213,214. However, it did not substantially reduce viral replication in SARS-CoV-infected mice, possibly because the cell surface pathway was not simultaneously blocked215. The anti-CoV effects, pharmacokinetic and pharmacodynamic profiles and toxicity of the combinations of different protease and endocytosis inhibitors that target these different cell entry pathways should be further evaluated in vivo.”

Review article stated it looks good in vitro, but 1 study in mice showed it did not ‘substantially’ reduce viral replication. But, do more studies...

The mouse study ( https://journals.sagepub.com/doi/pdf/10.1177/095632020601700505 ), starting last paragraph p279 “...intranasal chloroquine lessened viral lung titres by 0.8 half-log10 at the highest dose used, although this reduction was not statistically significant.”
So doing a repeat evaluation with a higher intranasal dose of chloroquine would be a possible avenue of study; especially as the intraperitoneal dose (in gut, typical administration route in mouse model) showed no effect. So, to me, maybe the drug was not getting to the site of action needed. Their discussion on p281, “As predicted by the in vitroexperiments in this study,agents such as nelfinavir and the marginally selectivechloroquine and amodiaquine, which have been suggestedby many who have reviewed the field of SARS antiviraltherapy (see, for example, Chihrin & Loutfy, 2005; Wuet al., 2006; De Clercq, 2006) to be promising antiviralagents for treating SARS, were not active in the mousemodel. The anti-inflammatory agents such as the chloro-quines and PTX are therefore presumed not to be likely tobe effective alone against a SARS infection.”