Cystatin D, a natural salivary cysteine protease inhibitor, inhibits coronavirus replication at its physiologic concentration

• This study was conducted to examine the effect of cystatin D, a newly discovered salivary cysteine protease inhibitor, on human coronavirus replication. When MRC-5, human diploid lung cells, were incubated with dilutions of recombinant human cystatin D from 0.65-10 microM for 1 h prior to, during and after infection with coronavirus OC43 and 229e strains, a decrease in virus yield was observed resulting in an IC50 of 0.8 microM for both virus strains. This dose is within the normal concentration range of cystatin D, 0.12-1.9 microM found in saliva. When a single dose, 2.5 microM, was applied, cystatin inhibition of release of virus progeny was not overcome until three days post infection whereas inhibition by leupeptin, a serine and cysteine protease inhibitor, was completely abrogated by two days. When cellular toxicity was measured by 3H-thymidine uptake, cystatin D did not markedly affect cell proliferation below a 10 microM dose. The results demonstrate that cystatin D is a potent inhibitor of coronavirus replication.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medicinal Chemistry (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

Coronavirus/drug effects

Coronavirus 229E, Human

Coronavirus OC43, Human

Cystatins/pharmacology

Cysteine Proteinase Inhibitors/pharmacology

Depression, Chemical

Dose-Response Relationship, Drug

Humans

Recombinant Proteins/pharmacology

Saliva/immunology

Time Factors

Virus Cultivation/methods

Virus Replication/drug effects

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)