Compendium of the most significant studies with reference to properties, intake, effects.
Drenth J, Jansonius JN, Koekoek R, Swen HM, Wolthers BG. Structure of papain. Nature. 1968 Jun 8;218(5145):929-32. doi: 10.1038/218929a0.
Abstract. A three-dimensional X-ray study at a resolution of 2.8 Å has revealed that the single polypeptide chain of 211 residues is folded into two distinct parts which are divided by a cleft.
Sáringer S, Akula RA, Szerlauth A, Szilagyi I. Papain Adsorption on Latex Particles: Charging, Aggregation, and Enzymatic Activity. J Phys Chem B. 2019 Nov 21;123(46):9984-9991. doi: 10.1021/acs.jpcb.9b08799.
Abstract. The effect of papain adsorption on the surface charge properties and aggregation mechanism of sulfate-functionalized polystyrene latex particles was studied. The positively charged enzyme possessed a high affinity to the oppositely charged particles, giving rise to charge neutralization and charge reversal at appropriate papain concentrations. The tendency in the particle aggregation rates at different enzyme doses revealed that the colloidal stability of the samples is governed by interparticle forces of electrostatic origin.
Yu D, Chen K, Liu J, Pan Z, Jiang L, Wang L, Elfalleh W. Application of magnetic immobilized papain on passivated rice bran lipase. Int J Biol Macromol. 2020 Aug 15;157:51-59. doi: 10.1016/j.ijbiomac.2020.04.132.
Abstract. Magnetically immobilized papain is prepared by magnetic Fe3O4/P (GMA-EDGMA-St) composite carrier with the addition of 12.0 mg/mL papain, 5.0% glutaraldehyde and 4 hour reaction time.
Vasconcelos NF, Cunha AP, Ricardo NMPS, Freire RS, Vieira LAP, Brígida AIS, Borges MF, Rosa MF, Vieira RS, Andrade FK. Papain immobilization on heterofunctional membrane bacterial cellulose as a potential strategy for the debridement of skin wounds. Int J Biol Macromol. 2020 Dec 15;165(Pt B):3065-3077. doi: 10.1016/j.ijbiomac.2020.10.200.
Abstract. We combined the chemical and physical methods of papain immobilization through the aldehyde groups available on oxidized bacterial cellulose (OxBC) to provide high proteolytic activity for future applications as bioactive dressing.
Leite AP, de Oliveira BG, Soares MF, Barrocas DL. Uso e efetividade da papaína no processo de cicatrização de feridas: uma revisão sistemática Use and effectiveness of papain in the wound healing process: a systematic review. Rev Gaucha Enferm. 2012 Sep;33(3):198-207. Portuguese. doi: 10.1590/s1983-14472012000300026.
Abstract. The articles showed that papain can be used in wounds of many etiologies and in various healing stages without any specific contraindications, proving to be effective and safe; although there were reports of burning and pain.
Sharma M, Sharma V, Panda AK, Majumdar DK. Development of enteric submicron particle formulation of papain for oral delivery. Int J Nanomedicine. 2011;6:2097-111. doi: 10.2147/IJN.S23985.
Abstract. Particulate systems have received increasing attention for oral delivery of biomolecules. The objective of the present study was to prepare submicron particulate formulations of papain for pH-dependent site-specific release using pH-sensitive polymers.
Gawlik K, Gutowicz J. Inhibitory activity against papain, a CA1 cysteine peptidase, in Saccharomycetaceae. Microbiol Res. 2008;163(5):545-55. doi: 10.1016/j.micres.2006.08.002.
Abstract. To gain insight into the endogenous inhibitors of CA1 cysteine peptidases in unicellular fungi, we initiated a study of the extra- and intracellular antipapain activity in yeast. We report here, for the first time, an analysis of the inhibitory activity against papain in the culture medium and the cell-free extract of 16 yeast strains belonging to the Saccharomycetaceae family. The existence of the antipapain activity, likely from protein inhibitors, in all the tested yeast strains has been demonstrated.
Khaparde SS, Singhal RS. Chemically modified papain for applications in detergent formulations. Bioresour Technol. 2001 May;78(1):1-4. doi: 10.1016/s0960-8524(00)00178-4.
Abstract. Papain was modified using succinic anhydride, and the modified papain so obtained was compared with the native papain for its activity and stability in detergents. This study was done using commercial enzyme detergents as references. It was found that modified papain retained activity comparable to the commercial enzyme detergents. Chemically modified papain may prove to be an inexpensive alternative to alkaline proteases that are used in detergents.
Lv Z, Cano KE, Jia L, Drag M, Huang TT, Olsen SK. Targeting SARS-CoV-2 Proteases for COVID-19 Antiviral Development. Front Chem. 2022 Feb 3;9:819165. doi: 10.3389/fchem.2021.819165.
Abstract. The emergence of severe acute respiratory syndrome (SARS-CoV-2) in 2019 marked the third occurrence of a highly pathogenic coronavirus in the human population since 2003. As the death toll surpasses 5 million globally and economic losses continue, designing drugs that could curtail infection and disease progression is critical. In the US, three highly effective Food and Drug Administration (FDA)-authorized vaccines are currently available, and Remdesivir is approved for the treatment of hospitalized patients. However, moderate vaccination rates and the sustained evolution of new viral variants necessitate the ongoing search for new antivirals. Several viral proteins have been prioritized as SARS-CoV-2 antiviral drug targets, among them the papain-like protease (PLpro) and the main protease (Mpro).
Papain 
