Препараты прямого противовирусного действия и блокирующие моноклональные антитела как основа этиотропной терапии новой коронавирусной инфекции

At the beginning of 2020, a pandemic of a novel coronavirus infection was declared in the world. Since the beginning of the pandemic, the search for drugs for etiotropic therapy as the basis for the treatment of the infectious process has begun. The review provides data on the application points of antiviral activity of drugs, taking into account the life cycle of the etiological agent – the SARS-CoV-2 virus. The mechanisms of drug action on RNA-dependent RNA polymerase (molnupiravir, remdesivir, favipiravir) and protease (nirmatrelvir together with ritonavir) SARS-CoV-2 are described. Among of outpatient patients at risk, the use of molnupiravir up to 5 days from the onset of the disease provided a 30% reduction in the risk of hospitalization and an 89% reduction in the risk of death. The use of a 10-day course of remdesivir in inpatient patients led to a reduction in the duration of clinical manifestations by 5 days, and the use of the drug for 3 days on an outpatient basis had a beneficial effect on a group of high-risk patients in the form of a reduction in the risk of hospitalization and death by 87%. Among outpatient patients using favipiravir, the onset of clinical improvement was noted 4 days earlier compared to the control group. The administration of nirmatrelvir in combination with ritonavir on an outpatient basis led to an 89% reduction in the risk of hospitalization or death. The molecular basis and principles of the use of blocking monoclonal antibodies as a fundamentally new group of biological drugs for etiotropic therapy are discussed. Information is provided on the effects of drugs on alpha, beta, gamma, delta and omicron variants of the virus. The profile of drug-drug interaction of drugs and basic therapy is analyzed. Early initiation of etiotropic therapy on an outpatient regime provides a more favorable course of the disease, which is characterized by a shorter duration of clinical manifestations, a reduced risk of hospitalization and the onset of death.В начале 2020 г. в мире была объявлена пандемия новой коронавирусной инфекции. С начала пандемии начались поиски препаратов для этиотропной терапии как основы лечения инфекционного процесса. В обзоре предоставлены данные о точках приложения противовирусной активности препаратов с учетом жизненного цикла этиологического агента – вируса SARS-CoV-2. Описаны механизмы воздействия препаратов на РНК-зависимую РНК-полимеразу (молнупиравир, ремдесивир, фавипиравир) и протеазу (нирматрелвир совместно с ритонавиром) SARS-CoV-2. Среди амбулаторных пациентов групп риска применение молнупиравира, назначенного до 5-го дня от начала заболевания, обеспечивало снижение риска госпитализации на 30% и риска смерти на 89%. Использование 10-дневного курса ремдесивира у стационарных больных приводило к сокращению продолжительности клинических проявлений на 5 дней, а использование препарата в течение 3 дней в амбулаторном режиме оказывало благоприятное влияние на группу больных высокого риска в виде снижения риска госпитализации и смерти на 87%. Среди амбулаторных пациентов, применявших фавипиравир, отмечалось наступление клинического улучшения на 4 дня раньше по сравнению с контрольной группой. Назначение нирматрелвира в сочетании с ритонавиром в амбулаторном режиме привело к уменьшению риска госпитализации или наступления летального исхода на 89%. Обсуждены молекулярная основа и принципы применения блокирующих моноклональных антител как принципиально новой группы биологических препаратов для этиотропной терапии. Представлена информация о воздействии препаратов на альфа-, бета-, гамма-, дельта- и омикрон-варианты вируса. Проанализирован профиль межлекарственного взаимодействия лекарственных средств и базисной терапии. Раннее начало этиотропной терапии в амбулаторном режиме обеспечивает более благоприятное течение заболевания, что характеризуется более короткой длительностью клинических проявлений, снижением риска госпитализации и наступления летального исхода

Clinical value of determination HIV viral load in the cerebrospinal fluid of HIV-infected patients

Aim. To analyze the concentration of HIV RNA in the cerebrospinal fluid and to evaluate its significance in the pathology of the central nervous system among HIV infected persons.Materials: We examined 36 patients with HIV infection with signs of pathology of the central nervous system. All patients was done completed a standard investigation of cerebrospinal fluid, cytological examination and detection viral load of HIV in the cerebrospinal fluid and serum.Results. A different of opportunistic and HIV-related disease was diagnosed in 29 patients. The most frequent pathology of the nervous system (12 cases) is a diffuse HIV-associated brain damage occurring in 7 patients in the form of aseptic non purulent meningitis and in 5 patients in the form of encephalitis. The average value of the absolute and relative count of CD4-lymphocytes in patients amounted 147,0 cells/μl (40,0; 408,75) and 10.0% (4,00; 18,50). Pathological changes in cellular composition and protein concentration of cerebrospinal fluid detected in 19 cases. Replication of HIV in the cerebrospinal fluid are detected in 31 of 32 patients not receiving antiretroviral therapy, including 17 patients with normal values of cerebrospinal fluid. The average HIV viral load in the cerebrospinal fluid was 15 133,0 copies/ml (2501,0; 30624,0) or 4,18 (3,35; 4,48) lg HIV RNA, average HIV viral load in serum – 62 784,0 copies/ml (6027,5; 173869,0) or 4,80 4,80 (3,7; 5,2) lg HIV RNA. The concentration of HIV in the cerebrospinal fluid was significantly lower than in serum (4,18 and 4,80 lg HIV RNA, p=0.027). 4 patients with severe, multietiology damage of the central nervous system viral, microbial and fungal etiology, there was an inverse relationship between the concentration of HIV in the cerebrospinal fluid and in serum, the concentrations of HIV was higher in the cerebrospinal fluid.Conclusion: Among the majority of HIV-infected patients with signs of the central nervous system pathology HIV replication in the cerebrospinal fluid was detected. Observed in some patients HIV replication in the cerebrospinal fluid in the absence of morphological and laboratory changes in the composition of cerebrospinal fluid may reflect indirect effects of HIV the brain, manifested in the form of functional disorders of the central nervous system

Regge Behavior of DIS Structure Functions

Building on previous works of the mid 1960's, we construct an integral equation for forward elastic scattering (t=0) at arbitrary virtuality Q^2 and large s=W^2. This equation sums the ladder production of massless intermediate bosons to all orders, and the solution exhibits Regge behavior. The equation is used to study scattering in a simple chi^2 phi scalar theory, where it is solved appoximately and applied to the study of DIS at small x. We find that the model can naturally describe the quark distribution in both the large x region and the small x region dominated by Reggeon exchange.Comment: 13 pages with 5 figure

DVCS amplitude at tree level: Transversality, twist-3, and factorization

We study the virtual Compton amplitude in the generalized Bjorken region (q^2 -> Infinity, t small) in QCD by means of a light-cone expansion of the product of e.m. currents in string operators in coordinate space. Electromagnetic gauge invariance (transversality) is maintained by including in addition to the twist-2 operators 'kinematical' twist-3 operators which appear as total derivatives of twist-2 operators. The non-forward matrix elements of the elementary twist-2 operators are parametrized in terms of two-variable spectral functions (double distributions), from which twist-2 and 3 skewed distributions are obtained through reduction formulas. Our approach is equivalent to a Wandzura-Wilczek type approximation for the twist-3 skewed distributions. The resulting Compton amplitude is manifestly transverse up to terms of order t/q^2. We find that in this approximation the tensor amplitude for longitudinal polarization of the virtual photon is finite, while the one for transverse polarization contains a divergence already at tree level. However, this divergence has zero projection on the polarization vector of the final photon, so that the physical helicity amplitudes are finite.Comment: 34 pages, revtex, 1 eps figure included using epsf. Misprints corrected, one reference adde

ПНЕВМОЦИСТНАЯ ПНЕВМОНИЯ КАК РЕДКОЕ КЛИНИЧЕСКОЕ ПРОЯВЛЕНИЕ ОСТРОЙ ВИЧ-ИНФЕКЦИИ

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Off-forward parton distributions and Shuvaev's transformations

We review Shuvaev's transformations, that relate off-forward parton distributions (OFPDs) to so-called effective forward parton distributions (EFPDs). The latter evolve like conventional forward partons. We express nonforward amplitudes, depending on OFPDs, directly in terms of EFPDs and construct a model for the EFPDs, which allows to consistently express them in terms of the conventional forward parton distributions and nucleon form factors. Our model is self-consistent for arbitrary x, xi, mu, and t.Comment: 13 pages, 7 eps-figures, LaTeX2e, added references, corrected typo

Probing partonic structure in gamma* gamma -> pi pi near threshold

Hadron pair production gamma* gamma -> h hbar in the region where the c.m. energy is much smaller than the photon virtuality can be described in a factorized form, as the convolution of a partonic handbag diagram and generalized distribution amplitudes which are new non-perturbative functions describing the exclusive fragmentation of a quark-antiquark pair into two hadrons. Scaling behavior and a selection rule on photon helicity are signatures of this mechanism. The case where h is a pion is emphasized.Comment: 8 pages, 1 figure, LaTeX2

Hard exclusive processes and higher-order QCD corrections

The short review of the higher order corrections to the hard exclusive processes is given. Different approaches are discussed and the importance of higher-order calculations is stressed.Comment: 17 pages; talk given at the 9th Adriatic Meeting, Dubrovnik 200

Unbiased analysis of CLEO data at NLO and pion distribution amplitude

We discuss different QCD approaches to calculate the form factor F^{\gamma^*\gamma\pi}(Q^2) of the \gamma^*\gamma\to\pi^{0} transition giving preference to the light-cone QCD sum rules (LCSR) approach as being the most adequate. In this context we revise the previous analysis of the CLEO experimental data on F^{\gamma^*\gamma\pi}(Q^{2}) by Schmedding and Yakovlev. Special attention is paid to the sensitivity of the results to the (strong radiative) \alpha_s-corrections and to the value of the twist-four coupling \delta^2. We present a full analysis of the CLEO data at the NLO level of LCSRs, focusing particular attention to the extraction of the relevant parameters to determine the pion distribution amplitude, i.e., the Gegenbauer coefficients a_2 and a_4. Our analysis confirms our previous results and also the main findings of Schmedding and Yakovlev: both the asymptotic, as well as the Chernyak--Zhitnitsky pion distribution amplitudes are completely excluded by the CLEO data. A novelty of our approach is to use the CLEO data as a means of determining the value of the QCD vacuum non-locality parameter \lambda^2_q = / =0.4 GeV^2, which specifies the average virtuality of the vacuum quarks.Comment: 25 pages, 5 figures, 4 tables; format and margins corrected to fit page size; small changes in the text and correction of misprint