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S svetovno pandemijo virusa SARS-CoV-2 se je pokazala potreba po učinkovitem zdravilu, saj možnosti cepljenja ob pojavu virusa še ni bilo. Kmalu po izbruhu epidemije na Kitajskem so začeli uporabljati rekonvalescentno plazmo prebolevnikov, relativno hitro pa so bila za uporabo potrjena tudi prva monoklonska protitelesa (mAb) proti SARS-CoV-2, kot so Bamlanivimab, Casirivimab in Imdevimab. Številna druga mAb za zdravljenje COVID-19 so še v razvoju, v postopkih odobritve ali pa tudi že na tržišču. Monoklonska protitelesa lahko delujejo na dva načina. Tista, ki so specifična za virus, oz. za protein S, nevtralizirajo virus SARS-CoV-2, ki se zato ne more pripeti na tarčne celice oz. na receptor ACE2. Druga skupina mAb pa so protitelesa, ki so specifična za citokine in v prejemniku sprožijo različne efektorske funkcije ter uravnavajo citokinsko nevihto. V večini so nevtralizirajoča mAb bolj učinkovita v začetnih stadijih bolezni, v poznejšem obdobju pa so bolj učinkovita mAb, ki zavirajo vnetne citokine. Največja omejitev in izziv pri razvoju za virus specifičnih nevtralizirajočih mAb so mutacije virusa na mestih, kjer mAb prepoznajo viruse, saj lahko s tem mAb postanejo neučinkovita. Zato je pomembno, da različicam sledimo in razvijamo učinkovita mAb, ki bi lahko zavarovala ljudi z visokim tveganjem za hujši potek bolezni in tiste, ki se zaradi zdravstvenih razlogov ne morejo cepiti. Since the global pandemic of the SARS-CoV-2 virus started, the need for an effective drug became apparent, since there was no possibility of vaccination when the virus appeared. Soon after the outbreak of the epidemic in China, the convalescent plasma of patients who had recovered began to be used, and relatively quickly the first monoclonal antibodies (mAb) against SARS-CoV-2, such as Bamlanivimab, Casirivimab and Imdevimab, were approved for use. Many other mAbs for the treatment of COVID-19 are still in development, in the approval process or already on the market. Monoclonal antibodies can work in two ways. Those that are specific to the virus, or for protein S, they neutralize the SARS-CoV-2 virus, which therefore cannot attach to target cells or to the ACE2 receptor. Another group of mAbs are cytokine-specific antibodies that trigger various effector functions in the recipient and regulate the cytokine storm. In most cases, neutralizing mAbs are more effective in the early stages of the disease, while mAbs that inhibit inflammatory cytokines are more effective in the later stages. The greatest limitation and challenge in the development of virus-specific neutralizing mAbs are mutations in the virus at sites where mAbs recognize viruses, as this can cause the ineffectivness of mAbs. Therefore, it is important to follow different variants of the virus and develop effective mAbs that could protect people with higher risk for more severe development of the disease and those who cannot be vaccinated for medical reasons. |
